Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer a solid milieu by inhibition of inflammatory reactions, which in turn, enables skin regeneration. Further, due to their great potential to stimulate angiogenesis and also facilitate matrix remodeling, MSCs hold substantial potential as future therapeutic strategies in this context. The MSCs-induced wound healing is thought to mainly rely on the secretion of a myriad of paracrine factors in addition to their direct differentiation to skin-resident cells. Besides, MSCs-derived exosomes as nanoscale and closed membrane vesicles have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of MSCs. The MSCs-derived exosomes comprise molecular components including lipid, proteins, DNA, microRNA, and also mRNA, which target molecular pathways and also biological activities in recipient cells (e.g., endothelial cell, keratinocyte, and fibroblast). The secreted exosome modifies macrophage activation, stimulates angiogenesis, and instigates keratinocytes and dermal fibroblast proliferations as well as migrations concurrently regulate inherent potential of myofibroblast for adjustment of turnover of the ECM. In the present review, we will focus on the recent findings concerning the application of MSCs and their derivative exosome to support wound healing and skin regeneration, with special focus on last decade in vivo reports.