Diabetes mellitus (DM) is one of the most important health problems with increasing prevalence worldwide. Oxidative stress that is a result of imbalance between reactive oxygen species (ROS) generation and antioxidant defense mechanisms has been demonstrated as a main pathology in DM. Hyperglycemia-induced ROS productions can induce oxidative stress through four major molecular mechanisms including, the polyol pathway, advanced glycation end-products formation, activation of protein kinase C isoforms, and the hexosamine pathways. In development of type 2 DM (T2DM) and its complications, genetic and environmental factors play important roles. Therefore, the aim of this review is to focus on assessment of single-nucleotide polymorphisms within antioxidant enzymes including superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, nitric oxide synthase, and NAD(P)H oxidase and their association with T2DM. The results will be helpful in understanding the mechanisms involved in pathogenesis of disease besides discovering new treatment approaches in management of DM.