Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world. Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265-8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116-5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071-4.969, P < 0.001), RAGE rs1800624 -374 T>A (OR 3.58, 95% CI 2.218-5.766, P < 0.001), and NOS3 -786 T>C (OR 3.75, 95% CI 2.225-6.666, P < 0.001). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554-44.804, P < 0.002). Our results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease.