The Hexane Extract (HE) and Ethyl Acetate Soluble Fraction of the Methanolic Extract (EASFME) of the fruit pulp of Momordica dioica Roxb. (Cucurbitaceae) was evaluated for its anti-hepatotoxic activity in rats. Acute hepatotoxicity was induced by administering paracetamol (2 g/kg, p.o.) for 3 days. The extracts, at a dose of 400 mg/kg (p.o.) administered for 7 days exhibited a significant therapeutic effect by lowering Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Serum Alkaline Phosphatase (ALP) and Serum bilirubin and increasing the serum protein levels. These biochemical observations were supplemented by histopathological examination of the liver sections. The activity of extract was also comparable to the standard drug Silymarin, which is a well-known natural anti-hepatotoxic drug.