Tissue engineering scaffolds have presented effective value in bone repair. However, the integration of the diverse components, complex structures, and multifunction to impart the scaffolds with improved applicability is still a challenge. Here, we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells (MSCs) to promote bone regeneration. The fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin (fGelMA), which can promote the proliferation and osteogenesis of MSCs with no obvious immunological rejection. Furthermore, the black phosphorus (BP) nanosheets are incorporated into the fGelMA hydrogel network, which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared (NIR) light. The fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in vitro. The regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and MSCs. These results suggest that the fish-derived scaffold, photothermal therapy, and MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.