: Evidence on the renal benefits and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the Asia region is still lacking. This study aimed to evaluate the renal and safety outcomes of SGLT2is compared with dipeptidyl peptidase-4 inhibitors (DPP4i) using real-world data. : A retrospective cohort study was conducted using the nationwide claims data in Republic of Korea. We evaluated kidney outcomes (any new-onset kidney events, acute kidney injury (AKI), chronic kidney disease (CKD), and kidney failure) as primary outcomes and safety outcomes (infection, hemodynamic adverse events, and fracture). Propensity score matching was used to adjust confounders, and the hazard ratios were calculated using the Cox proportional hazards model. : The study included 13,649 patients in the SGLT2i group and 35,043 in the DPP4i group after the matching. The SGLT2i group had a lower risk of kidney diseases, AKI, and CKD (HR 0.88 [0.61-0.74]) than the DPP4i group. For secondary outcomes, the risk of genital infection was higher (HR 2.38 [2.12-2.68]), and the risk of hyperkalemia was lower in the SGLT2i group than in the DPP4i group (HRs 0.49 [0.36-0.67]). : The SGLT2 inhibitors had a lower risk of new-onset kidney outcomes and CKD than the DPP4 inhibitors. A high incidence of genital infection and a low incidence of hyperkalemia were shown in the SGLT2 inhibitor.