Mesenchymal stem cells (MSCs) have emerged as promising cell therapy agents for promoting skin healing and regeneration. MSCs, with their multipotent differentiation capabilities, can generate various cells involved in wound healing, such as dermal fibroblasts, endothelial cells, and keratinocytes. They also promote neovascularization, cellular regeneration, and tissue healing through paracrine and autocrine signaling mechanisms. MSCs have been extensively studied in burn healing and chronic wound repair, and their unique roles in skin aging and scarless healing have also been discovered. This review summarizes the mechanisms by which MSCs promote wound healing, discusses recent findings from preclinical and clinical studies, and explores strategies to enhance their therapeutic effects. The integration of MSCs with tissue engineering techniques, such as biodegradable scaffolds and hydrogels, is highlighted as a promising approach to enhance skin repair capacity. Additionally, the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies is discussed, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.Mesenchymal stem cells (MSCs) have emerged as promising cell therapy agents for promoting skin healing and regeneration. MSCs, with their multipotent differentiation capabilities, can generate various cells involved in wound healing, such as dermal fibroblasts, endothelial cells, and keratinocytes. They also promote neovascularization, cellular regeneration, and tissue healing through paracrine and autocrine signaling mechanisms. MSCs have been extensively studied in burn healing and chronic wound repair, and their unique roles in skin aging and scarless healing have also been discovered. This review summarizes the mechanisms by which MSCs promote wound healing, discusses recent findings from preclinical and clinical studies, and explores strategies to enhance their therapeutic effects. The integration of MSCs with tissue engineering techniques, such as biodegradable scaffolds and hydrogels, is highlighted as a promising approach to enhance skin repair capacity. Additionally, the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies is discussed, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.