Hemostasis is the initial step in wound healing, yet significant challenges, such as massive bleeding and infection, often arise. In this study, we developed amphiphilic biodegradable polyester-based segmented polyurethane (SPU) microspheres modified with epigallocatechin gallate (EGCG)-Ag nanoparticles and calcium-alginate cross-linking shell, combining blood absorption with the pro-coagulation properties of Ca2+ and the negative charge of EGCG for synergistic hemostatic effects across various stages of the coagulation cascade. The in vitro blood clotting time of the SPU@EAg@CaAlg microsphere (328.7 s) was reduced by half compared to the SPU microsphere (685.0 s). SPU@EAg@CaAlg exhibited a reduced hemostatic time and blood loss in three rat hemostatic models. Additionally, EGCG-Ag nanoparticles imparted strong antibacterial and anti-inflammatory properties both in vitro and in vivo. In vivo infected wound model demonstrated that SPU@EAg@CaAlg effectively eliminated bacteria and reduced the levels of pro-inflammatory factors, thereby promoting wound healing. Thus, the modified SPU microspheres present a promising candidate for effective hemostatic applications.