Background. Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders. However, little is known regarding the effect of antioxidant SNPs on renal events. Methods. We prospectively enrolled multicenter patients with end-stage renal disease (ESRD) and those without chronic kidney disease (CKD) of Han Chinese origin, with SOD2 (Val16Ala), GPX1 (Pro197Leu), and PPAR-γ (Pro12Ala, C161T) genotyped. Multiple regression analyses were conducted to evaluate the significant risk determinants for ESRD. Results. Compared to ESRD patients, non-CKD subjects were more likely to have T allele at SOD2 Val16Ala (p = 0.036) and CC genotype at PPAR-γ Pro12Ala (p = 0.028). Regression analysis showed that TT genotype of SOD2 Val16Ala conferred significantly lower ESRD risk among patients without diabetes (odds ratio 0.699; p = 0.018). GPX1 SNP alone did not alter the risk. We detected significant interactions between SNPs including PPAR-γ Pro12Ala, C161T, and GPX1 regarding the risk of ESRD. Conclusion. This is the first and largest study on the association between adverse renal outcomes and antioxidant SNPs among Han Chinese population. Determination of SOD2 and PPAR-γ SNPs status might assist in ESRD risk estimation.