Background: Carbon tetrachloride (CCl4 ) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis. Lepidium sativum contains flavonoids, alkaloids, and antioxidant components. Objectives: This study aims to investigate the hepatic protection of L. Sativum Extract (LSE) on CCl4 -induced hepatotoxicity in mice.  Methods: A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4 , and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis. Results: Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P<0.05), AST in all doses (P<0.001), and ALP in 600 mg/kg (P<0.001). In addition, LSE treatment significantly increased GSH in 400 mg/kg (P<0.01) and 600 mg/kg (P<0.001). Conclusion: LSE has hepatic protective activity against CCl4 -induced injuries. The possible anti-hepatotoxic mechanisms may be related to the presence of flavonoids, triterpenes, alkaloids, tannin, and coumarins in the LSE by inhibiting the free radicals mediated damage.