Benadryl is quickly absorbed after oral administration and it starts to work within 30 minutes with peak effects reached within one to two hours. The effects of Benadryl last from four to six hours. Benadryl in the injectable form has a rapid onset of action. You will know when Benadryl starts to work because your allergy symptoms, such as congestion, runny nose, itchy eyes, or a skin rash, will start to feel better.