Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes of patients with type 2 diabetes at high cardiovascular risk and chronic kidney disease. Recent studies showed an increase in hemoglobin and hematocrit after SGLT2i treatment. Materials and methods We did a systematic review and meta-analysis of randomized, double-blind, placebo-controlled studies of SGLT2i in patients with type 2 diabetes. We searched through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from January 2010 to January 2021. Results We included seventeen randomized, double-blind, placebo-controlled studies. The total number of evaluated patients was 14,748. The treatment arm consisted of canagliflozin, dapagliflozin, empagliflozin and ipragliflozin. SGLT2i therapy significantly increased hemoglobin levels when compared to placebo (MD 5.60 g/L, 95% CI 3.73-7.47 g/L, P < 0.00001, considerable heterogeneity-I-2 = 94%). Each SGLT2i also led to a significant increase in the hematocrit level when compared to placebo (MD 1.32%, 95% CI 1.21-1.44, P < 0.00001, considerable heterogeneity-I-2 = 99%). Conclusions SGLT2i led to significant increases in hemoglobin and hematocrit levels when compared to placebo. In addition to their cardiovascular effect, SGLT2i also increases hemoglobin and hematocrit levels.