In Ayurveda, Cissus quadrangularis Linn. is used to treat anorexia, asthma, sickle cell, colds, pain, and malaria. Aqueous C. quadrangularis extract was evaluated in vivo for its antiepileptic activity by using the maximal electroshock and isonicotinic hydrazide acid models, for its analgesic activity by using the hot plate method, and for its smooth muscle relaxant activity by using the rotarod method. Adult male Swiss mice were used for this study and animals were divided into 6 animals per group. Doses of 250 mg/kg body weight and 500 mg/kg body weight protected the mice against maximal electroshock seizure, and delayed the onset time of seizures induced by isonicotinic hydrazide acid. Prominent analgesic activity was observed using the hot plate method. The paw licking time was delayed significantly. The extract also displayed prominent smooth muscle relaxant activity. The results suggest that the aqueous extracts of C. quadrangularis roots possess anticonvulsant, analgesic, and smooth muscle relaxant properties.