In this study, the neuroprotective potential and in vivo antioxidant status of extract of roots and rhizomes of Rubia cordifolia L (MERC) in reserpine-induced orofacial dyskinesia was studied. Reserpine (1 mg/kg, s.c.) on day 1, 3 and 5 was used to induce orofacial dyskinesia. At the end of treatment schedule, MERC significantly inhibited reserpine-induced vacuous chewing movements, tongue protrusions, orofacial bursts, catalepsy. MERC significantly increased locomotion and rearing in open field test. MERC exhibited significant elevation in the levels of superoxide dismutase, catalase, glutathione reductase and inhibition of lipid peroxidation in forebrain region, compared with the reserpine treated group. It significantly elevated dopamine levels in the forebrain region. GCMS revealed the presence of anthraquinones, having strong antioxidant activity. It is concluded that oxidative stress might play an important role in reserpine-induced abnormal oral movements and MERC significantly protected animals against reserpine-induced orofacial dyskinesia and has great potential in treatment of neuroleptic induced orofacial dyskinesia.