Recently, a new class of antidiabetic drugs, dipeptidyl peptidase-IV (DPP-4) inhibitors, has gained considerable interest in different fields. In addition to lower glucose and improve insulin resistance, DPP-4 inhibitors have exhibited pleiotropic effects, including cardioprotection, angiogenesis, hematopoiesis recovery and inflammation inhibition via the regulation of the substrates, such as glucagon-likepeptide-1 (GLP-1), stromal cell-derived factor-1α (SDF-1α), vascular endothelial growth factor (VEGF) and high mobility group box 1 (HMGB1) etc. The role of DPP-4 in cardiovascular disease has been fully reported by previous studies, so the goal of this review is focused on the function and mechanism of DPP-4 and its inhibitors in vascular regeneration, and developing a better understanding of the drugs.