The methanolic extract of Grewia mollis leaves was evaluated in vivo for its antioxidant and hepatoprotective properties. Oxidative stress was induced in rats by administering carbon tetrachloride (CCl(4)) intraperitoneally at a dose of 0.6 mL/kg, whereas the crude plant extract and standard antioxidant (vitamin E) were administered at a dose of 5 mg/kg and 50 mg/kg, respectively. The effect of G. mollis crude extracts and vitamin E on malondialdehyde (MDA) and liver function parameters such as protein, bilirubin, aspartate aminotransferase, and alanine aminotransferase were measured spectrophotometrically. The methanolic extract of G. mollis leaves and vitamin E showed a significant (P<.05) hepatoprotective potential by lowering the serum levels of bilirubin, aspartate aminotransferase, and alanine aminotransferase and decreasing MDA levels in rats pretreated or post-treated with CCl(4). Based on these results, it is concluded that G. mollis leaves contain potent antioxidant compounds that could offer protection against hepatotoxicity as well as ameliorate preexisting liver damage and oxidative stress conditions.