Wound healing is a dynamic process occurring in multiple interdependent stages that include a regulated interaction between different cell types, extracellular matrix, proteases and their substrates. Increasing scientific evidence emphasizes the importance of proteases playing crucial roles in the regulation of processes of wound healing. Dipeptidyl peptidase IV (DPP IV/CD26, EC 3.4.14.5), the main member of the DPP IV family of proteins, is a ubiquitous multifunctional transmembrane as well as soluble glycoprotein, acting as a proteolytic and costimulation molecule, and binding protein. It is expressed on the surface different cell types, including epithelial, endothelial cells and lymphocytes. It has been shown to play a significant role in different physiological as well as pathological processes. DPP IV/ CD26 was largely investigated given its ability to maintain glucose homeostasis. Moreover, since positive effects of DPP IV/CD26 inhibition in healing of chronic diabetic foot ulcers as well as other pathologies have been shown, growing efforts are made in order to elucidate its mechanisms of action. It is known that DPP IV/CD26 is involved in the regulation of cell adhesion, migration, apoptosis, angiogenesis and extracellular matrix degradation, which are all key processes in wound healing. Previous studies indicated that DPP IV/CD26 plays a particularly relevant role in skin regeneration where it was found to mediate inflammatory processes and influence epithelialization of wounds. Therefore, the aim of this review was to summarize crucial findings regarding wound healing as well as new insights about the involvement of DPP IV/CD26 in tissue regeneration.