Abstract: Dimethoate (DM), an organophosphate insecticide, has been used worldwide in agriculture and domestic for several years which has led to a variety of negative effects in non target species including humans. Therefore, the present study investigated the ameliorative properties of vitamin C (vitC) and E (vitE) on DM toxicity of guinea pigs. The animal groups were orally administered with either vehicle, vitC (200 mg kg^-1 body weight) and vitE (200 mg kg^-1 body weight), 1/50 LD₅₀ of DM (7 mg kg^-1 b.w.) and 1/50 LD₅₀ of DM + vitC and vitE daily for 28 days. Administration of DM resulted in a significant increase in the levels of various serum marker enzymes (AST ALT and ALP). Similarly, significant increase in Lipid Peroxidation (LPO) level while induced significant decreases in the activities of liver Catalase (CAT) and Glutathione-S-Transferase (GST). In contrast, co-administration of vitC and vitE to DM-treated animals restored most of these biochemical parameters to nearly normal levels. Also, DM induced histopathological alterations such as cytoplasmic vacuolization and degeneration in nuclei, congestion, an enlargement of the blood vessels and lymphocytes infiltration in the liver. These changes were ameliorated by vitamins co-administration. The results showed that co-treatment of vitE and vitC protected guinea pigs from DM-induced biochemical and histopathological changes.