In this study, ternary organic–inorganic composite bone cements of tricalcium silicate/sodium alginate/calcium sulfate hemihydrate (C₃S/SA/CS) were successfully fabricated for in vitro and in vivo osteogenesis study, mainly including proliferation, attachment and osteogenic differentiation of mouse bone marrow mesenchymal stem cells, and bone regeneration in critical-sized rabbit femoral condyle defect model. Bone marrow mesenchymal stem cells treated with the C₃S/SA/CS composite cements exhibited good proliferation, excellent attachment, enhanced alkaline phosphatase activity, increased calcium deposition, and osteogenic-related gene expressions with increasing calcium sulfate component. Depending on optimally combinatorial effect of bioactive calcium and silicon ions in osteogenic differentiation, the C3 composite cement (C₃S/SA/CS: 35/35/30 wt%, inorganic content: 65 wt%) with moderate surface wettability and suitable environmental pH possessed more remarkable osteogenic activity as compared with other compositions of composite cements. Furthermore, in vivo results of micro-CT analysis and histological evaluation confirmed that the C3 composite cement with enhanced cell attachment and osteogenic differentiation could induce much more bone formation and better osseointegration in comparison with the C0 composite cement (C₃S/SA/CS: 50/50/0 wt%). Therefore, the C3 composite cement with significantly improved osteogenesis capacity might have certain potential as bioactive implantable materials for bone regeneration.