Exacerbation of osteolysis in osteoporotic bone defects presents a significant challenge for implant-based treatments. This underscores the urgent need to develop implants that actively mitigate osteolysis while simultaneously promoting bone regeneration. In this study, the osteogenic potential of mesoporous bioactive glass (MBG) and β-tricalcium phosphate (β-TCP) was combined with the anti-bone resorption property of Ga doping. Ga-MBG was synthesized using a self-transformation method and subsequently incorporated into β-TCP at concentrations of 5 wt%, 10 wt% and 15 wt%. Scaffolds were prepared using extrusion-based 3D printing. The cytocompatibility of the composite scaffolds and their regulatory effects on the differentiation of osteoblasts and osteoclasts were systematically examined. In addition, the molecular mechanisms underlying bone regeneration and osteolysis regulation in osteoblasts were explored. Subsequently, cranial defects were repaired in a rat model of osteoporosis to assess the therapeutic efficacy and biological safety of the optimal concentration of the Ga-MBG/TCP composite scaffold. These findings indicated that the 10 wt% Ga-MBG/TCP composite scaffold exhibited excellent biocompatibility, enhanced new bone formation, and effectively mitigated osteolysis. These results provide a foundation for further investigation into the optimal concentration of Ga-MBG implants and highlight their potential application in future therapies for osteoporotic bone defects.