Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca2+, promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.