<PAGE>

                                                                     Exhibit 3.1

                                  AMENDED AND

                     RESTATED CERTIFICATE OF INCORPORATION

                                      OF

                              ADOLOR CORPORATION


          ADOLOR CORPORATION, a corporation duly organized and existing under
the General Corporation Law of the State of Delaware (the "Corporation"), was
incorporated under the name Opian Pharmaceuticals, Inc., and its original
Certificate of Incorporation was filed with the Secretary of State of the State
of Delaware on August 9, 1993.

          This Amended and Restated Certificate of Incorporation has been duly
adopted by the stockholders of the Corporation in accordance with the provisions
of Section 242 and 245 of the General Corporation Law of the State of Delaware.

          FIRST:   The name of the corporation is Adolor Corporation.

          SECOND:  The registered office of the Corporation in the State of
Delaware is to be located at 2711 Centerville Road, Suite 400, City of
Wilmington, County of New Castle, Delaware, 19808.  The name of the registered
agent of the corporation at such address is The Prentice-Hall Corporation
System, Inc.

          THIRD:   The purpose of the Corporation is to engage in any lawful act
or activity for which a corporation may be organized under the General
Corporation Law of the State of Delaware, as amended from time to time.

          FOURTH:  The total number of shares of all classes of capital stock
which the Corporation shall have authority to issue is 100,000,000 shares,
consisting of 99,000,000 shares of Common Stock with a par value of $.0001 per
share (the "Common Stock") and 1,000,000 shares of Preferred Stock with a par
value of $.01 per share (the "Preferred Stock").

          A description of the respective classes of stock and a statement of
designations, powers, preferences and rights, and the qualifications,
limitations and restrictions of the Preferred Stock and Common Stock are as
follows:

          A.   COMMON STOCK
               ------------

          1.   General.  All shares of Common Stock will be identical and will
               -------
entitle the holders thereof to the same rights, powers and privileges.  The
rights, powers and privileges of the holders of the Common Stock are subject to
and qualified by the rights of holders of the Preferred Stock.
<PAGE>

          2.   Dividends.  Dividends may be declared and paid on the Common
               ---------
Stock from funds lawfully available therefor as and when determined by the Board
of Directors and subject to any preferential dividend rights of any then
outstanding Preferred Stock.

          3.   Dissolution, Liquidation or Winding Up.  In the event of any
               --------------------------------------
dissolution, liquidation or winding up of the affairs of the Corporation,
whether voluntary or involuntary, each issued and outstanding share of Common
Stock shall entitle the holder thereof to receive an equal portion of the net
assets of the Corporation available for distribution to the holders of Common
Stock, subject to any preferential rights of any then outstanding Preferred
Stock.

          4.   Voting Rights.  Except as otherwise required by law or this
               -------------
Amended and Restated Certificate of Incorporation, each holder of Common Stock
shall have one vote in respect of each share of stock held of record by such
holder on the books of the Corporation for the election of directors and on all
matters submitted to a vote of stockholders of the Corporation.  Except as
otherwise required by law or provided herein, holders of Common Stock shall vote
together with holders of the Preferred Stock as a single class, subject to any
special or preferential voting rights of any then outstanding Preferred Stock.
There shall be no cumulative voting.


          B.   PREFERRED STOCK
               ---------------

          1.   Issue in Series.  Preferred Stock may be issued from time to time
               ---------------
in one or more series, each such series to have the terms stated herein and in
the resolution of the board of directors of the Corporation providing for its
issue.  All shares of any one series of Preferred Stock will be identical, but
shares of different series of Preferred Stock need not be identical or rank
equally except insofar as provided by law or herein.

          2.   Creation of Series.  The board of directors will have authority
               ------------------
by resolution to cause to be created one or more series of Preferred Stock, and
to determine and fix with respect to each series prior to the issuance of any
shares of the series to which such resolution relates:

               2A.  The distinctive designation of the series and the number of
shares which will constitute the series, which number may be increased or
decreased (but not below the number of shares then outstanding) from time to
time by action of the board of directors;

               2B.  The dividend rate and the times of payment of dividends on
the shares of the series, whether dividends will be cumulative, and if so, from
what date or dates;

               2C.  The price or prices at which, and the terms and conditions
on which, the shares of the series may be redeemed at the option of the
Corporation;

                                      -2-
<PAGE>

               2D.  Whether or not the shares of the series will be entitled to
the benefit of a retirement or sinking fund to be applied to the purchase or
redemption of such shares and, if so entitled, the amount of such fund and the
terms and provisions relative to the operation thereof;

               2E.  Whether or not the shares of the series will be convertible
into, or exchangeable for, any other shares of stock of the Corporation or other
securities, and if so convertible or exchangeable, the conversion price or
prices, or the rates of exchange, and any adjustments thereof, at which such
conversion or exchange may be made, and any other terms and conditions of such
conversion or exchange;

               2F.  The rights of the shares of the series in the event of
voluntary or involuntary liquidation, dissolution or winding up of the
Corporation;

               2G.  Whether or not the shares of the series will have priority
over or be on a parity with or be junior to the shares of any other series or
class in any respect or will be entitled to the benefit of limitations
restricting the issuance of shares of any other series or class having priority
over or being on a parity with the shares of such series in any respect, or
restricting the payment of dividends on or the making of other distributions in
respect of shares of any other series or class ranking junior to the shares of
the series as to dividends or assets, or restricting the purchase or redemption
of the shares of any such junior series or class, and the terms of any such
restriction;

               2H.  Whether the series will have voting rights, in addition to
any voting rights provided by law, and, if so, the terms of such voting rights;
and

               2I.  Any other preferences, qualifications, privileges, options
and other relative or special rights and limitations of that series.

          3.   Dividends.  Holders of Preferred Stock shall be entitled to
               ---------
receive, when and as declared by the board of directors, out of funds legally
available for the payment thereof, dividends at the rates fixed by the board of
directors for the respective series, and no more, before any dividends shall be
declared and paid, or set apart for payment, on Common Stock with respect to the
same dividend period.

          4.   Preference on Liquidation.  In the event of the voluntary or
               -------------------------
involuntary liquidation, dissolution or winding up of the Corporation, holders
of each series of Preferred Stock will be entitled to receive the amount fixed
for such series plus, in the case of any series on which dividends will have
been determined by the board of directors to be cumulative, an amount equal to
all dividends accumulated and unpaid thereon to the date of final distribution
whether or not earned or declared before any distribution shall be paid, or set
aside for payment, to holders of Common Stock.  If the assets of the Corporation
are not sufficient to pay such amounts in full, holders of all shares of
Preferred Stock will participate in the distribution of assets ratably in
proportion to the full amounts to which they are entitled or in such order or
priority, if any, as will have been fixed in the resolution or resolutions
providing for the issue of

                                      -3-
<PAGE>

the series of Preferred Stock. Neither the merger nor consolidation of the
Corporation into or with any other corporation, nor a sale, transfer or lease of
all or part of its assets, will be deemed a liquidation, dissolution or winding
up of the corporation within the meaning of this paragraph except to the extent
specifically provided for herein.

          5.   Redemption.  The Corporation, at the option of the board of
               ----------
directors, may redeem all or part of the shares of any series of Preferred Stock
on the terms and conditions fixed for such series.

          6.   Voting Rights.  Except as otherwise required by law, or as
               -------------
otherwise determined by the board of directors as to the shares of any series of
Preferred Stock prior to the issuance of any such shares, the holders of
Preferred Stock shall have no voting rights and shall not be entitled to any
notice of any meeting of stockholders.

          FIFTH:    The Corporation shall have perpetual existence.

          SIXTH:    The number of directors of the Corporation shall be such as
from time to time shall be fixed by, or in the manner provided, in the by-laws
of the corporation.  No election of directors need be ballot unless the by-laws
so provide.

          SEVENTH:  To the fullest extent that the general corporate law of the
State of Delaware, as it exists on the date hereof or as it may hereafter be
amended, permits the limitation or elimination of the liability of the
directors, no director of the Corporation shall be liable to the Corporation or
its stockholders for monetary damages for breach of fiduciary duty as a
director.  No amendment to or repeal of this Article shall apply to or have any
effect on liability or alleged liability of any director of the Corporation for
or with respect to any acts or omissions of such director occurring prior to
such amendment or repeal.

          EIGHTH:   The Corporation shall, to the fullest extent permitted by
subsection 145 of the General Corporation Law of the State of Delaware, as the
same may be amended and supplemented, indemnify any and all persons whom it
shall have power to indemnify under said section from and against any and all of
the expenses, liabilities, or other matters referred to in or covered by said
section, and the indemnification provided for herein shall not be deemed
exclusive of any other rights to which those indemnified may be entitled under
any by-law, agreement, vote of stockholders, or disinterested directors or
otherwise, both as to action in their official capacity and as to action in
another capacity while holding such office, and shall continue as to a person
who has ceased to be a director, officer, employee, or agent and shall inure to
the benefit of the heirs, executors, and administrators of such a person.

                                      -4-
<PAGE>

          NINTH:   The Board of Directors shall have power without the assent or
vote of the stockholders to make, alter, amend, change, add to or repeal the by-
laws of the Corporation.


Dated: March 22, 2001                        ADOLOR CORPORATION


                                             By: /s/ Peter J. Schied
                                                -------------------------
                                                Peter J. Schied
                                                Secretary

                                      -5-