Back Ground: Cypermethrin (CPM) is non-systematic type II synthetic pyrethroid, commonly used for pest control in livestock, forestry, horticulture, household, public and animal health services, private homes, and animal husbandry. By scavenging free radicals and modulating antioxidant protection mechanism, plant phytochemicals (vitamin C and Curcumin) are known to exert their protective impact, Aim: The current research aimed to examine the ameliorative effect of combining curcumin with prevention of vitamin C against the toxic effects of cypermethrin. Method: Four groups of ten male rats each, –ve control, +ve control group (200 mg curcumin and 100 mg vit. C/ kg bw), cypermethrin alone (200 mg / Kg bw), and cypermethrin supplemented with the protective antioxidants orally intubated for 28 - days. Result: Oral cypermethrin induced a significant increase in MDA and PC in serum, liver and brain as the oxidant biomarkers. While the antioxidant biomarkers (CAT, GSH or SH protein) were significantly decreases in serum and brain tissues. The phase II biotransformation GST was increased significantly in brain and liver tissues. ATPase activity declined significantly in brain tissue only. Conclusion: we can deduce that, cypermethrin induce oxidative stress in serum and organs tissues of male rats and the protective role curcumin and vit. C was more evident on serum, brain than liver.