Development of bioactive scaffolds with controllable architecture and high osteogenic capability for bone tissue engineering is hotly pursued. In this study, three-dimensional (3D) mesoporous bioactive glass (MBG) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds with well-defined pore structures and high compressive strength (∼5-12 MPa) were synthesized by a 3D printing technique. Compared to reported polymer-bonded MBG scaffolds, the incorporation of the biocompatible PHBHHx polymer as a particle binder enhanced their bioactive and osteogenic properties, including fast apatite-forming ability, and promoted human bone marrow-derived mesenchymal stem cell (hBMSC) adhesion, proliferation, alkaline phosphatase (ALP) activity and bone-related gene expression. Furthermore, MBG/PHBHHx composite scaffolds were explored to repair critical-size rat calvarial defects. The results showed that MBG/PHBHHx composite scaffolds exhibited a controlled degradation rate and more significant potential to stabilize the pH environment with increasing PHBHHx ratio. At 8 weeks post-implantation, MBG/PHBHHx scaffolds were demonstrated to stimulate bone regeneration in the calvarial defects and have largely repaired them through analysis of micro-CT, sequential fluorescent labeling and histology. These results lay a potential framework for future study by using modified MBG/PHBHHx-based functional scaffolds to improve the osteogenic activity and bone defect restoration.