Currently, there is increasing attention towards flavonoids and phenolic compounds of plant origin because of their association with decrease in the incidence of cardiovascular diseases and different types of cancer. The present study investigates the protective effect of Clerodendrum volubile (C. volubile) methanolic extracts against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Control rats (group I) received olive oil (1 mL/kg, i.p.), group II received CCl₄ in olive oil (1 ml/kg, i.p.) to induce hepatotoxicity, groups III, IV and V were pretreated with leaf extract of C. volubile at 125 mg/kg, 250 mg/kg and 500 mg/kg body weight respectively for 14 days prior to CCl₄ administration, group VI received vitamin E (100 mg/kg, p.o.) as standard antioxidant to compare with antioxidant effects of the extract. CCl₄ hepatotoxicity, characterized by significant (P < 0.05) increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), hepatic degeneration, and inflammation was attenuated by C. volubile methanolic extracts. The serum lipid parameters which include high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly (P < 0.05) decreased, and increased respectively by CCl_4. Methanolic extracts of C. volubile significantly prevented the decrease in the level of HDL and the increase in LDL in a dose-dependent manner (P < 0.05). Decrease in total protein induced by CCl₄ was moderately increased following administration of methanolic extracts of C. volubile. Lipid peroxidation was significantly (P < 0.05) reduced while the reduced glutathione (GSH) level and the activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were significantly elevated by C. volubile extract in the CCl₄-treated rats. Our findings indicate that C. volubile extract has a significant protective effect against CCl₄-induced hepatotoxicity in rats which may be due to its antioxidant properties which is comparable to the reference antioxidant, vitamin E, used in this study.