Skin wound healing is a complex biological process. Mesenchymal stem cells (MSCs) play an important role in skin wound repair due to their multidirectional differentiation potential, hematopoietic support, promotion of stem cell implantation, self-replication, and immune regulation. Exosomes are vesicles with diameters of 40-100 nm that contain nucleic acids, proteins, and lipids and often act as mediators of cell-to-cell communication. Currently, many clinical scientists have carried out cell-free therapy for skin wounds, especially chronic wounds, using exosomes derived from MSCs. This review focuses on the latest research progress on the mechanisms of action associated with the treatment of wound healing with exosomes derived from different MSCs, the latest research progress on the combination of exosomes and other biological or nonbiological factors for the treatment of chronic skin wounds, and the new prospects and development goals of cell-free therapy.