Dimethoate (DM) is one type of organophosphorus insecticide, that kills insects and mites both systemically and immediately upon contact and harms a range of non-target animals, including fish when it enters the aquatic habitat. This study aimed to determine the potentially harmful histopathological and biochemical impacts of Dimethoate on Nile tilapia fish. Sixty Oreochromis Niloticus freshwater fish, each weighing an average of 130 ± 10 g, were divided into two groups in triplicates. There were 6 groups, 3 control groups, and 3 experiment groups that received Dimethoate at a dose of 8 mg/l in water for 15 days. Blood samples were collected and used for biochemical indexes. For histological analysis, samples of the brain, gills, liver, and kidney were collected. The findings of the study demonstrated that fish treated with Dimethoate exhibited pale gills, anxious symptoms, as well as congestion and hemorrhages in many internal organs, comprising the brain, kidney, and liver. There was a significant increase in the blood levels of nitric oxide, lipid peroxide, and glutathione peroxidase and a significant fall in catalase levels in the Dimethoate group when compared to the control group. Pesticides, especially DM, should not be used carelessly in agriculture and allowed to accumulate in streams because of deleterious effects on fish.