Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been recognized as potent antioxidant agents. Since SGLT2i are nephroprotective drugs, we aimed to examine the urine antioxidant status in patients with type 2 diabetes mellitus (T2DM). One hundred and one subjects participated in this study, including 37 T2DM patients treated with SGLT2i, 31 T2DM patients not using SGLT2i, and 33 healthy individuals serving as a control group. Total antioxidant capacity (TAC), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), free thiol groups (R-SH, sulfhydryl groups), and catalase (CAT) activity, as well as glucose concentration, were assessed in the urine of all participants. Urine SOD and MnSOD activity were significantly higher among T2DM patients treated with SGLT2i than T2DM patients without SGLT2i treatment ( p = 0.009 and p = 0.003 , respectively) and to the healthy controls ( p = 0.002 and p = 0.001 , respectively). TAC was significantly lower in patients with T2DM treated with SGLT2i when compared to those not treated and healthy subjects ( p = 0.036 and p = 0.019 , respectively). It could be hypothesized that the mechanism by which SGLT2i provides nephroprotective effects involves improvement of the SOD antioxidant activity. However, lower TAC might impose higher OS (oxidative stress), and elevation of SOD activity might be a compensatory mechanism.