Objective: The dipeptidyl peptidase 4 (DPP4) inhibitors have been widely used for treating the patients with diabetes as a potent anti-hyperglycemic control, along with the reduction of cardiovascular risk. The recent studies have identified that several DPP4 inhibitors including sitagliptin and anagliptin have the beneficial effect on atherosclerosis and neointimal hyperplasia in addition to glucagon-like peptide 1 (GLP1) augmentation. Therefore, we hypothesized that DPP4 inhibition by gemigliptin can attenuate the abnormal vascular remodeling by interfering with the proliferation and migration of vascular smooth muscle cells (VSMCs), directly. Methods: Aortic ligation injury, H&E staining, WST assay, Flow cytometry analysis, Western, PCR, Zymography, Migration assay, and Immunofluorescence staining Results: Gemigliptin significantly prevented the neointimal hyperplasia induced by ligation injury in mouse carotid arteries, in vivo. Likewise, the proliferation of rat primary VSMCs stimulated by 20% FBS was significantly attenuated by gemigliptin in a dose dependent manner, confirmed by the decreased phospho-Rb leading to G1 cycle cell arrest, consequently. We found that gemigliptin enhanced Nrf2 activity by not only its mRNA expression but also increased Keap1 proteosomal degradation by p62, resulting in the induction of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 and heme oxygenase 1. The anti-proliferative role of gemigliptin disappeared in VSMCs with DPP4 siRNA knockdown, revealing that the endogenous DPP4 in VSMCs mediated the effect of gemigliptin. Besides, gemigliptin diminished TNF-α-mediated cell adhesion molecules such as MCP-1, VCAM-1 and MMP2 activity in VSMCs. Conclusion: Taken together, our data suggest that gemigliptin can have the prohibitory effect on the proliferation and migration of VSMCs beyond the incretin effect, leading to the prevention of abnormal vascular remodeling.