Oxidative stress by increased production of reactive oxygen species has been implicated in pesticides toxicity. This study focused on the toxicological effects of chlorpyrifos, an organophosphate insecticide and abamectin, a biocide each alone or in combination on antioxidant status, and oxidative stress biomarkers in brain and kidney. Animals were divided into four groups. The first group was used as control while groups 2, 3, and 4 were treated with chlorpyrifos (CPF; 14.9 mg/kg BW), abamectin (ABM; 30 mg/kg BW), and chlorpyrifos plus abamectin, respectively. Rats were treated daily with the tested compounds by oral gavages for 30 days. Results revealed that thiobarbituric acid-reactive substances (TBARS) levels were significantly increased in brain and kidney due to insecticides administration. On the other hand, reduced glutathione (GSH) and protein contents in addition to the activities of antioxidant enzymes, alkaline phosphatase (ALP), and acetylcholinesterase (AChE) were significantly decreased in rat organs. A significant induction in lactate dehydrogenase (LDH) activity, urea, and creatinine levels were also observed. The response was more pronounced in rats treated with both CPF and ABM. Results showed that the used insecticides had the propensity to cause significant oxidative damage in rat brain and kidney which is associated with marked perturbations in antioxidant defense system. It can be concluded that antioxidant enzymes can be used as potential biomarkers of toxicity associated with pesticides exposure.