The present study was aimed to investigate the hepatoprotective and antioxidant activities ofethanol extract from Monochoria vaginalis (250 mg/kg and 500 mg/kg B/W) on acetaminophen (APAP)induced rat hepatic injury. Monochoria vaginalis is a traditional medicinal plant that is commonlyused to treat and improve liver conditions in India and other Asian countries. The developmentof hepatotoxicity induced by APAP is promoted by oxidative stress. APAP treated groupsignificantly (P < 0.01) elevated the serum enzymatic levels like glutamate oxaloacetatetransaminase, glutamate pyruvate transaminase, alkaline phosphatase (SALP), total bilirubin andmalondialdehyde (MDA), which were restored towards normalization significantly (P < 0.01)thanol extract of yonochoria vagin is (EEMV). In addition, the EEMV significantly (P < 0.01)elevated the decreased level of total protein and antioxidant enzymes such as superoxidedismutase, catalase, glutathione peroxidase, glutathione-s-transferase and reduced glutathione.Apart from these, histopathological changes also showed the protective nature of the EEMVagainst APAP induced hepatic damage in liver tissues. The activity of EEMV at 500 mg/kg B/Wwas comparable to the standard drug silymarin (25 mg/kg B/W). In conclusion, these datasuggest that the EEMV possess hepatoprotective and antioxidant effects against APAP-inducedhepatotoxicity and oxidative stress in rats.