The present study was carried out to evaluate the protective role of aqueous extract of Mentha spicata (MSE) leaf on dichlorvos (DDVP) induced oxidative stress in rat brain. Male rats were divided into 4 groups, the first group served as control (C). Group (E1) received 5.33mg/Kg BW of DDVP and group (E2) received 5.33mg/Kg BW of DDVP with MSE (100.0 mg/kg) and the group (E3) received MSE (100.0 mg/kg). Rats under all the groups were treated with their respective constituents for 30 days. The results suggested that rats under E1 suffered from significant (p<0.01) decline in the activity of superoxide dismutase, catalase, glutathione peroxidase with a significant elevation in the levels of malondialdehyde of their brain. Histological changes were also found to be prominent in the brain of E1 group as compared to others. Rats under E2 showed recuperation tendencies which were evidenced by partial restoration of antioxidant enzyme activity and the lesser degree of damage in histological aspect as compared to E1. No significant changes were observed in either biochemical constituents or histological aspects of rats under E3. The current study suggests that DDVP can cause oxidative damage and brain injury in male rats and co-administration of MSE with the selected dose partially attenuates the toxic effect caused by DDVP