The present study aimed to evaluate the effect of sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin therapy on the prooxidant-antioxidant balance (PAB) in patients with diabetic kidney disease. Methods. A total of 88 patients with type 2 diabetes mellitus (DM) and diabetic nephropathy (DN) were included in this single-center randomized open-label prospective study. All patients were randomly divided into 2 groups: 45 patients received a standard course of treatment, which included antidiabetic drugs, renin-angiotensin-aldosterone system blockers, and HMG-CoA reductase inhibitors (statins). In addition to the standard therapy, the remaining 43 patients were prescribed the SGLT2 inhibitor dapagliflozin 10 mg per day. Patients were re-examined after 6 months of treatment. The blood PAB was calculated as the ratio of total hydroperoxides (THP) to total antioxidant activity (TAA). The level of THP and TAA was determined by the colorimetric method. Results. PAB was significantly elevated in type 2 DM patients with nephropathy due to TAA decrease and THP level increase when compared to the control group. The highest values of PAB were found in the late stages of DN in patients with glomerular filtration rates <60 ml/min/1.73m2. In patients who received dapagliflozin, significant PAB elevation by 30,55% (р < 0.05) was observed as well as THP decrease and TAA increase in blood. In the standard therapy group, no significant changes in PAB parameters were detected. Conclusions. Add-on treatment with dapagliflozin resulted in a more significant improvement of the PAB in patients with DN in comparison with standard treatment.