Objective: To investigate the therapeutic effect of liraglutide combined with glimepiride on diabetes mellitus. Methods: 66 patients with diabetes from March 2017 to April 2019 in our hospital were selected as research objects, and were divided into two groups according to different treatment schemes. The control group used conventional scheme, while the observation group used liraglutide combined with glimepiride scheme to compare the therapeutic effects of the two groups. Results: after medication, the postprandial 2h blood glucose level, glycosylated hemoglobin level and fasting blood glucose level of the two groups in this study are lower than those obtained in this study before medication. the values obtained in the observation group in this study are lower than those obtained in the control group in this study, which are statistically significant (p < 0.05). Conclusion: Liraglutide combined with glimepiride is effective in the treatment of diabetes mellitus and is worthy of application.