This investigation aimed to evaluate the toxic effects of permethrin (PMN) on rat liver and the therapeutic efficacy of curcumin (CMN) against PMN-induced alterations in hepatic biomarkers, liver antioxidant enzymes, and SK-Hep-1 cells. The animals were divided into four groups of six as follows: the first group was defined as the control, while the second, the third, and the fourth groups were orally treated with PMN (62.5 mg/kg bw), CMN (120 mg/kg bw), and PMN plus CMN, respectively for three weeks. Biochemical markers in the serum and the levels of lipid peroxidation (LPO) and antioxidant enzyme activity in the liver were determined. PMN exposure stimulated significant changes in animals' hepatic biomarkers, including alanine and aspartate aminotransferases (ALT and AST) and alkaline phosphatase (ALP). The results indicated that LPO was significantly raised in PMN-treated rats, as evidenced by high liver malondialdehyde (MDA) concentration. The antioxidant system in PMN-treated rats was altered, which confirmed by a significant decline (p<0.05) in the activity of catalase (CAT), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) in the liver. On the other hand, the administration of CMN with PMN significantly (p<0.05) ameliorated ALT, AST, ALP, MDA, CAT, GPX, and GST activity. In addition, CMN demonstrated protective activity against toxicity induced by PMN in SK-Hep-1 cells. In conclusion, our findings demonstrated that PMN induced hepatic damage in rats and CMN had noticeable therapeutic effects on hepatic injuries, oxidative stress, and cytotoxicity induced by PMN.