Abstract Fish skin grafting as a new skin substitute is currently being used in clinical applications. Acceleration of the wound healing, lack of disease transmission, and low cost of the production process can introduce fish skin as a potential alternative to other grafts. An appropriate decellularization process allows the design of 3D acellular scaffolds for skin regeneration without damaging the morphology and extracellular matrix content. Therefore, the role of decellularization processes is very important to maintain the properties of fish skin. In this review article, recent studies on various decellularization processes as well as biological, physical, and mechanical properties of fish skin and its applications with therapeutic effects in wound healing were investigated.