Herein, strontium (Sr) was successfully doped into strontium-containing calcium sulfate/poly(amino acid) (CS/PAA) composites to develop a novel bioactive bone graft, whose degradability, biocompatibility, and bioactivity were investigated in vitro and in vivo. Compared to CS/PAA composites, Sr-CS/PAA composites showed a slower degradation rate, such that, approximately, 20% less mass was lost at the end of the in vitro degradation tests. Moreover, strontium was gradually released into the degradation media along with the degradation of Sr-CS/PAA composites. In vitro, MC3T3-E1 cells adhered well on the Sr-CS/PAA composites, and the optical density values showed no significant difference between Sr-CS/PAA groups and CS/PAA groups on days 4 and 7. However, the alkaline phosphatase activity of the Sr-CS/PAA groups was significantly higher than that of the CS/PAA groups. The in vivo osteogenesis of Sr-CS/PAA composites was evaluated in rabbit femoral condyle critical bone defects. The results confirmed that Sr-CS/PAA composites exhibited superior capacity of repair for bone defects than CS/PAA composites. Taken together, Sr-CS/PAA composites were demonstrated as promising candidates for bone regeneration, showing appropriate degradation rate, superior biocompatibility and biological activity.