Aims: Evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and glimepiride, a sulfonylurea, have been used to treat type 2 diabetes mellitus. This study aimed at evaluating the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride. Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or co-administration of the two (EVO+GLI). Serial blood and urine samples for PK and PD analyses were collected 168 and 24 hours post-dosing, respectively. Results: Thirty-four subjects completed the study. Co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (C_max,ss) and the area under the curve during dosing interval at steady-state (AUC_τ,ss) of EVO+GLI to E were 1.02 (0.98 – 1.06) and 0.97 (0.95 – 1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01 – 1.17) and 1.08 (1.02 – 1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.80 – 1.25. Administration of EVO+GLI decreased the glucose excursion compared to evogliptin and glimepiride monotherapy, respectively. Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while combination therapy showed an additive glucose lowering effect compared to those of evogliptin or glimepiride monotherapy.