According to the complementary advantages of the composites, the degradation rate, biological activity and physical and chemical properties of the composites were adjusted by using the hydrophilic and bioactive advantages of soy protein isolate (SPI) on the basis of toughening PLA by polycaprolactone (PCL). In this study, soy protein isolate/polylactic acid–polycaprolactone (SPI/PLA–PCL) composite microspheres were fabricated via double emulsion–solvent evaporation. SPI was introduced to regulate hydrophilicity, biodegradation, and bioactivity based on PCL–toughened PLA. The microspheres were characterized by SEM, EDS, FTIR, and XRD. Hydrophilicity, thermal stability, and degradation behavior were evaluated via water contact angle, TG/DTA, and in vitro degradation assays. Biocompatibility, hemocompatibility, and osteogenic activity were assessed through cell adhesion, hemolysis, CCK–8, ALP, alizarin red staining, and mineralization tests. Results confirmed the successful preparation of SPI/PLA–PCL microspheres. SPI incorporation enhanced hydrophilicity, degradation rate, and cell adhesion. The composite microspheres exhibited favorable thermal stability, hemocompatibility, biocompatibility, and osteogenic induction. The 50% SPI/PLA–PCL group performed optimally in cell proliferation, adhesion, ALP activity, and mineralization, demonstrating promising potential for bone tissue engineering applications.