Recently, it is proposed that oxidant- antioxidant imbalance may have a role in the pathophysiology of schizophrenia. The present study was performed to assess differences in plasma levels of Malondialdehyde (MDA), as an oxidant product, antioxidant such as superoxide dismutase (SOD), reduced glutathione (GSH), vitamin E (__ampersandsignalpha;-tocopherol), vitamin C (ascorbic acid) etc., and total antioxidant capacity(TAC) in the patients with schizophrenia as compared with healthy controls. Our secondary aim was to further evaluate the effect of combined supplementation of antioxidant vitamins E and C along with antipsychotics treatment on these parameters. The study includes prospective, double blind, non-crossover, and 12 weeks intervention of antioxidants. Plasma levels of MDA, erythrocytes SOD, GSH, vitamin E, vitamin C and TAC levels in plasma in patients with schizophrenia before (n=40) and after regular antipsychotic treatment (n=20) and treatment with antipsychotics plus antioxidant E and C supplementation (n=20) were compared with healthy controls (n=40). The levels of MDA were significantly increased in patient before treatment while the levels of SOD, GSH, vitamin E and C and TAC in plasma shown significant reduction. However, the antioxidant supplementation along with antipsychotics reverses the above levels. PANSS (positive and negative syndrome scale) change scores at 12 weeks improved statistically significant with antioxidant E and C supplementation as compared to alone antipsychotics treatment. So oral supplementation of antioxidants in combination reduces oxidative stress and improves clinical symptoms suggest the application of antioxidant in clinical trials is beneficial to prevent or reduces the progression of disease.