Background: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). However, the effectiveness of these drugs in large populations is unclear. Subjects and Methods: As of May 2020, data analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Review and Assessment Service database in Korea. Using the COVID-19 and claims data of the past 5 years, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Results: Totally, data of 67850 subjects were accessible. Of these, 5080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP-4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 [95% confidence interval (CI), 0.135-0.971], and that for RAS blockade users was 0.599 (95% CI, 0.251-1.431). No synergy was observed for subjects using both drugs. Conclusion: This population-based study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19. However, the effect of RAS blockade is not significant.