In the present study the methanol extract of Gynocardia odorata roxb (MEGO) against acetaminophen induced hepatotoxicity and anti- oxidant activity in Wistar albino rats was analysed. The methanol extract of G.odorata roxb (200, and 400 mg/kg body weight) was administered orally to two groups of rats (six animals per group) in order to evaluate the protective effect of the extract in rats. The other three groups were received normal saline (2 ml/kg), acetaminophen (750 mg/kg), and silymarin (50 mg/kg) respectively. The anti-oxidant effect of the extract on serum marker enzymes and histopathological studies of liver was assessed. The plant extract (200 and 400 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against acetaminophen induced hepatotoxicity. Histopathological changes of liver sample shows mild hepatocyte degeneration. Results indicate that the G.odorata roxb possesses significant hepatoprotective and antioxidant property. Thus the study substantiates its use in traditional herbal medicine.