Emamectin benzoate (EMB) is a biopesticide that is used in agriculture as an insecticide. Due to its wide range of use, it is easier to reach ecologically and affects human health. This study aims to evaluate the protective effect of natural compounds against EMB-induced hepatotoxicity. It is the first study quantifying the hepatoprotective effect of these extracts against EMB effects. Biochemical analysis includes MDA, CAT, SOD, ALT and AST analysis. However, genetic studies include the gene expression of Mgst1, CYP2E1, caspase3, IL-1β and DNA fragmentation, as well as, histopathological investigations were performed. Male mice were distributed into five groups: G1: the negative control, G2: EMB group (5mg/kg diet), G3: EMB+Boswellia serrata (90 mg/kg diet), G4: EMB+Cinnamomum zeylanicum (600mg/kg diet), G5: EMB+ powder of the snail (600mg/kg diet), and the experiment continues for eight weeks. The results appeared that EMB induced oxidative stress in the liver by increase the activity of MDA. The biomarker of liver injury ALT and AST were elevated with antioxidant enzymes inhibition. EMB produced several histopathological changes in the liver. Relative expressions of Mgst1, CYP2E, caspase-3 and IL-1β genes elevated in the liver. The increase in DNA damage was noticed as recorded by an increase in tail length, tail DNA% and tail moment. Co-treatment with natural compounds reduced the toxicity of EMB. They reduce the abnormal biochemical, histopathological, gene expression and DNA damage by increasing antioxidant capacity. Therefore, the natural compounds used in this study act as potent hepatoprotective agents against EMB induced hepatotoxicity in mice