S. Muralidhar began his law practice in Chennai in September 1984. He qualified as a Company Secretary in December 1985. In July 1987 he shifted his practice to Delhi where he initially worked as a junior lawyer to the then Additional Solicitor General G Ramaswamy, who would later become the Attorney General for India. Muralidhar primarily practiced in the Supreme Court of India and the Delhi High Court. He qualified the Advocate-on-Record Examination in 1990 securing the first position in merit and was awarded the Mukesh Goswami Memorial Prize. He was also active as a lawyer for the Supreme Court Legal Services Committee and later was its member for two terms. His "pro bono" work included the cases for the victims of the Bhopal Gas Disaster, cases involving the deplorable conditions in which persons alleged to be mentally ill were locked up in Jail and cases involving those displaced by the dams on the Narmada. He was appointed amicus curiae by the Supreme Court in several Public Interest Litigation cases and in cases involving convicts on death row. Muralidhar was counsel for the National Human Rights Commission and the Election Commission of India and a part-time member of the Law Commission from December 2002 till May 2006.