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Background: The hyperglycemia-induced oxidative stress in diabetes mellitus (DM) is the major factor in the pathogenesis of cardiovascular complications. The phenolic compounds are potent antioxidants that can reverse the factors leading to cardiovascular complications in DM. The aim of this study was to determine the antagonizing effects of a polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid, on oxidative stress in Type 2 diabetic patients., Materials and Methods: A total of 114 male and female non-smokers (56 study, 58 placebo) with Type 2 DM and without any complications were recruited. The blood levels of fasting blood glucose, glycated hemoglobin, LDL, HDL, triglycerides, plasma malondialdehyde (MDA), total glutathione (GSH), hydrogen peroxide, and antioxidant capacity (AOC) were determined at the beginning and at the end of the 3-month trial. The differences of the data changes between the groups were statistically analyzed by Mann-Whitney U test., Results: The study group showed a decrease in LDL and an increase in HDL and the comparison with the difference in placebo group was statistically significant (p<0.001 for LDL and p<0.001 for HDL). Accordingly, as a by-product of lipid peroxidation, plasma MDA was decreased in the study group compared to the placebo group (p<0.001). As an indicator of increased antioxidant defense, total plasma GSH and AOC increased more in the study group compared to control group (p<0.001)., Conclusions: These observations indicated that the polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid has important antagonizing effects on oxidative stress and lipid peroxidation in patients with Type 2 DM and might be beneficial in preventing cardiovascular complications.