Abstract Various requirements for the repair of complex bone defects have motivated to development of scaffolds with adjustable degradation rates and biological functions. Tricalcium phosphate (TCP) and calcium sulfate are the most commonly used bone repair materials in the clinic, how to better combine TCP and calcium sulfate and play their greatest advantages in the repair of osteoporotic bone defect is the focus of our research. In this study, a series of scaffolds with multistage-controlled degradation properties composed of strontium-doped calcium sulfate (SrCSH) and strontium-doped tricalcium phosphate (Sr-TCP) microspheres scaffolds were prepared, and their osteogenic activity, in vivo degradation and bone regeneration ability in tibia of osteoporotic rats were evaluated. In vitro studies revealed that different components of SrCSH/Sr-TCP scaffolds significantly promoted the proliferation and differentiation of MC3T3-E1 cells, which showed a good osteogenic induction activity. In vivo degradation results showed that the degradation time of composite scaffolds could be controlled in a large range (6–12 months) by controlling the porosity and phase composition of Sr-TCP microspheres. The results of osteoporotic femoral defect repair showed that when the degradation rate of scaffold matched with the growth rate of new bone, the parameters such as bone mineral density, bone volume/total volume ratio, trabecular thickness, angiogenesis marker platelet endothelial cell adhesion molecule-1 and new bone formation marker osteocalcin expression were higher, which promoted the rapid repair of osteoporotic bone defects. On the contrary, the slow degradation rate of scaffolds hindered the growth of new bone to a certain extent. This study elucidates the importance of the degradation rate of scaffolds for the repair of osteoporotic bone defects, and the design considerations can be extended to other bone repair materials, which is expected to provide new ideas for the development of tissue engineering materials in the future.