Abstract: Background and Objective: Most medicinal plants presently employed in traditional medicine are used without scientific evaluation. In this study, the hepatoprotective potential of the aqueous extract of Senna mimosoides leaves was investigated on Wistar albino rats to ascertain its efficacy and to scientifically validate its traditional use. Materials and Methods: A total of 30 Wistar Albino rats of the same sex were used and grouped as follows: Group A (control) were administered 0.2 mL of normal saline only, other rats in groups B, C, D were treated with 50, 100 and 250 mg kg–1 of aqueous extract of Senna mimosoides, respectively, group E received 25 mg kg–1 of silymarin, a standard hepatoprotective drug while group F served as the positive control. Carbon tetrachloride was used to induce hepatotoxicity in all the groups except group A. Results: There was a significant dose-dependent decreases (p<0.05) in the enzymatic activities of AST aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). However, result showed significant dose-dependent increases (p<0.05) in the enzymatic activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). In addition, enzymatic effects (whether increases or decreases) observed in the group that was treated with 250 mg kg–1 of extract were more than that of the group that was treated with 25 mg kg–1 of silymarin a standard hepatoprotective drug. Conclusion: Based on the results obtained from this study, it was concluded that the leaves of Senna mimosoides possessed antihepatotoxic effect.