: Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) -25.39%, 95% confidence interval (CI) -34.17 to -16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD -40.78%, 95% CI -63.21 to -18.34) or severely increased albuminuria (WMD -36.40%, 95% CI -51.53 to -21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI -5.24 to -3.63) and 1.81 mmHg (95% CI -2.38 to -1.23), respectively.