Background: Bivalves are known as a healthy nutrition choice due to the highest amounts of nutrients which has antioxidants, anti-inflammatory, and anti-apoptotic effects. lithophaga Lithophaga is one of the major bivalves which had been reported as a vital medical nutrient.  Aim: This work aimed to evaluate the potential activity of L. lithophaga extract (ELE) against carbon tetra chloride (CCl₄)-induced liver fibrosis in mice. Material and Methods: Forty adult male mice were used in this study, they were divided into four groups:  control, ELE (0.5 mg/Kg), CCl₄ (4 mg/kg, twice weekly, for 4 weeks) and CCl₄ for 4 weeks then treatment with ELE for consecutive 4 weeks. Results: The obtained results revealed that ELE improved the activity of antioxidants; SOD, CAT, and GPx that disrupted by CCl₄. This was associated with restoration of liver deleterious histopathological features induced by CCl₄. The levels of liver indices (ALT, AST and Alb) are markedly improved. Moreover, ELE downregulated the expression of P53, Caspase-3 and TNF-α in the liver upregulated by CCl_{4 .} This reflects the anti-apoptotic and inflammatory markers. Conclusion: Lithophaga lithophaga extract has a powerful ameliorative role against liver fibrosis via modulation of anti-oxidants, liver functions, and histopathological signs caused by CCl₄.