Present study was conducted to check the effect of lemon peel extract (LPE) against SA (Sodium Arsenite)- induced liver toxicity that results in dysfunction of liver due to increase in oxidative stress. HPLC analysis with C18 column was used to analyze hesperidin content in lemon peel at 280nm. Antioxidant potential of hesperidin was analyzed via efficacy for this purpose. Sprague dawely rats were divided into 5 groups (n=30). Liver toxicity was induced by consuming 10 mg sodium arsenic per kilogram of rat body weight. Different concentrations of LPE were introduced to each experimental unit. Effectiveness of doses were analyzed by biochemical parameters. Blood samples were collected at different intervals to estimate the serum ALT (Alanine aminotransferase), AST (Aspartate aminotransferase), MDA (Malondialdehyde), SOD (Superoxide dismutase), CAT (Catalase) and GPx (Glutathione peroxidase) level. Lemon peel extract had 16.5430 mg/100g hesperidin. Serum ALT (38.16±1.25 U/L), AST (31.67±3.06) and MDA (2.68±0.01) level was significantly lowered after LP extract consumption as compared with SA-induced liver toxicity group (38.16±1.25), (97.16±4.58) respectively. While serum SOD (163.17±1.25 U/mL), CAT (112.0±1 U/mL) and GPx (3.12±0.017 MU/L) level was significantly higher after LP extract consumption as compared with disease group (78.00±0.50 U/mL), (74.0±1.0 U/mL) and (0.83±0.04 MU/L) respectively. Present study demonstrated that lemon peel has potential to attenuate SA-induced liver toxicity and oxidative stress that directly correlated to its pharmacological properties based on polyphenol (especially hesperidin dominant flavonoid) content. Lemon peel extract has great potential against oxidative stress and related disorders. There is dire need to attain an appropriate method for extraction of lemon peel extract to get its maximum benefits.