The general aim of this study is to assess the effects of fractionated methanolic leaf extract of Gongronema latifoliumon CCl4-induced wistar albino rats. Fifty-four (54) Wistar albino rats were divided into seven treatment groups. Group A was given feed and water, Group B was injected with olive oil intra peritoneally, while the rest of the groups (C, D, E, F and G) were injected intra peritoneally with a single dose of CCl4(148 mg/kg). After 36 hours of induction, group E, F and G were given 100 mg/kg, 150 mg/kg and 200 mg/kg body weight of n-butanol fraction of methanol leaf extract of Gongronema latifolium by oral gavage. Group D was given 100 mg/kg of silymarin (standard drug) whereas group C served as CCl4-induced group. At the end of 28 days of treatment, there were significant (P < 0.05) reduction in PCV, Hb concentration and serum protein levels as well as a significant (P < 0.05) increase in percentage change in liver weights of CCl4-induced control rats when compared with the induced treated groups. Liver marker enzymes studies showed that there was significant (P < 0.05) increase in the serum activities of ALT, AST, ALP and bilirubin concentrations in CCl4-induced control group when compared with the induced treated groups. Antioxidant assay on the liver homogenate showed that there was significant (P < 0.05) decrease in SOD, CAT, GPx and a significant increase (P < 0.05) in MDA of CCl4-induced control rats when compared to the normal control rats. These findings suggested that n-butanol fraction of methanol leaf extract of G. latifolium may have anti-hepatotoxic and antioxidative effects against CCl4-induced liver damage rats.