The association between the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and the occurrence of drug-induced kidney injury has not been evaluated. This study assessed whether the use of SGLT-2 inhibitors decreases the risk of drug-induced acute kidney injury (AKI) using the US Food and Drug Administration's Adverse Event Reporting System and the Medical Data Vision database. The occurrence of AKI in SGLT-2 inhibitor users and dipeptidyl peptidase-4 (DPP-4) inhibitor users was compared using both databases. In the US Food and Drug Administration's Adverse Event Reporting System analysis, disproportionality for AKI was observed between DPP-4 inhibitor users and SGLT-2 inhibitor users administered nonsteroidal anti-inflammatory drugs (reporting odds ratio, 0.65; 95%CI, 0.48-0.88; P < .01) and thiazide diuretics (reporting odds ratio, 0.78; 95%CI, 0.67-0.90; P < .01). In Medical Data Vision analysis, SGLT-2 inhibitor users administered nonsteroidal anti-inflammatory drugs (odds ratio [OR], 0.46; 95%CI, 0.41-0.53; P < .01), anti–herpes simplex virus drugs (OR, 0.20; 95%CI, 0.07-0.53; P < .01), thiazide diuretics (OR, 0.50; 95%CI, 0.36–0.71, P < .01), and loop diuretics (OR, 0.71; 95%CI, 0.62-0.83; P < .01) had a lower incidence of AKI compared with DPP-4 inhibitor users receiving the same drugs. No differences were observed in the risk of AKI between SGLT-2 and DPP-4 inhibitor users administered vancomycin and cisplatin in both databases. The use of SGLT-2 inhibitors might reduce the risk of drug-induced AKI caused by some drugs.