Liver diseases still represents a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases, including liver disease. Clidemia hirta possesses many medicinal properties for healing several diseases and for health maintenance. However, the hepatoprotective effects and antioxidative potential of C. hirta have not been fully investigated. In the present study, we evaluated the hepatoprotective and antioxidative potential of C. hirta against carbon tetrachloride (CCl4)-induced liver injuries and oxidative damage in a murine model. Various biochemical changes associated with liver damage and oxidative stress were measured. The mice were pretreated for 14 consecutive days with aqueous extract of C. hirta at selected doses (150 mg/kg body weight [b.w.], 300 mg/kg b.w. and 600 mg/kg b.w.) followed by two doses of CCl4 (1.0 mL/kg b.w.) orally on days 14 and 15. All animals were sacrificed 24 hours after the last dose of CCl4 or saline. Blood and liver tissues were taken quickly for biochemical and histopathological studies to assess the derangement in the functioning of liver. The development of oxidative stress was observed through the escalation of hepatic lipid peroxidation, depletion of glutathione, and reduced antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, glutathione S-transferase and quinone reductase). Hepatic damage was evaluated by measuring serum transaminase (ALT and AST). In addition, CCl4-induced hepatic damage was further evaluated using histopathological assessments. However, most of these changes were dependently ameliorated by the pretreatment of mice with a C. hirta dose. These results indicate that the hepatoprotective effect of C. hirta might be due to its antioxidant and free-radical scavenging properties.