Rapid bone defect regeneration in osteoporotic conditions remains a significant challenge due to the fragile mechanical stability and pathological microenvironment. The absence of bone matrix is the primary characteristic of these defects, and advanced strategies for treating osteoporotic bone defects focus on remodeling the bone matrix's spatial structure and regulating the microenvironment. While many hydrogels have been developed for bone regeneration, their use in repairing osteoporotic bone defects is constrained by deficiencies in shape-adaptivity, weak osteogenic bioactivity, and lack of physiological mechanical support. Herein, a novel bioactive hydrophilic semi-caged NH2-T4 silsesquioxane (NH2-T4-POSS) nanocage was developed, which was used to modify γ-polyglutamic acid (γ-PGA) together with dopamine, to give an organic/inorganic hybrid hydrogel PGA-DA&T4 for osteoporotic bone regeneration. The developed PGA-DA&T4 hydrogel possesses favorable injectability, shape-adaptivity, self-healability, and strong antioxidant ability. Benefited from organic/inorganic hybridation and multidimensional molecular interacting mechanism, PGA-DA&T4 exhibites enhanced thermal stability and longer degradation period, unique self-polymerizability, high elasticity, and considerable tissue adhesion ability. In vitro experiments proved that PGA-DA&T4 is biocompatible, and is able to promote cell migration and neovascularization, and possesses favorable immunoregulatory to promote macrophage polarization towards anti-inflammatory M2 phenotype. Furthermore, PGA-DA&T4 has been demonstrated to accelerate osteogenic differentiation and inhibit osteoclastogenesis, thereby promoting the repair of osteoporotic bone defects. Our research successfully developed a novel hybrid γ-PGA hydrogel with therapeutic effects and supplied a promising biomaterial with potential clinical application for repairing osteoporotic bone defects.