Abstract: The aim of the present study was to evaluate effect of ellagic acid, a polyphenol bioactive compound, on reserpine-induced orofacial dyskinesia in Wistar male albino rats and to explore the possible underlying mechanisms for this effect. Reserpine (1 mg kg–1, i.p.) was administered on every alternate day for a period of 5 days (day 1, 3 and 5) to induce orofacial dyskinesia in rats. Ellagic acid (10, 20 and 40 mg kg–1, po) was administered for 15 successive days (from 6th-20th day) to separate groups of reserpine treated rats. Reserpine increased vacuous chewing movements, indicating induction of orofacial dyskinesia. It also decreased locomotor activity of rats. Ellagic acid significantly reversed reserpine-induced vacuous chewing movements and hypolocomotion in rats and significantly ameliorated reserpine-induced oxidative stress, as indicated by decrease in brain lipid peroxidation and increase in brain reduced glutathione, catalase and superoxide dismutase activities. Ellagic acid significantly attenuated reserpine-induced orofacial dyskinesia, probably through alleviation of oxidative stress. Thus, ellagic acid may be explored further for its potential in management of tardive dyskinesia.