Poly(lactide-co-glycolide) (PLGA) copolymers are promising synthetic materials in the biomedical field. However, in wound management, their hydrophobic properties limit their further application because of their poor adhesion to the surface of moist wounds. Furthermore, the lack of hemostatic materials with sustainable anti-infection and immunoregulation functions remains a highly significant clinical problem, as commercially available hemostatic products, such as Arista™, Celox™ and QuikClot™, do not have sufficient infection prevention and immunoregulation properties. Herein, we employ electrospinning, ammonia dissociation and surface grafting techniques to develop a series of PLGA-based hemostatic materials, including a PLGA electrospun fibrous membrane, PLGA-NH2 fibrous particles and PLGA-hyaluronic acid fibrous fragments (PLGA-HA FFs). Notably, we load azithromycin on the PLGA-HA FFs to endow them with anti-infection and immunoregulation properties. The hemostatic mechanism analysis demonstrates that the PLGA-HA FFs show superior hemostasis performance compared to traditional gauzes. The results show that the PLGA-HA FFs can act as a versatile platform with high encapsulation of azithromycin (83.03% ± 2.81%) and rapid hemostasis (28 ± 2 s) as well as prominent cytocompatibility towards L929 cells, RAW 264.7 cells and red blood cells. We believe that the current research proposes a possible strategy to synthesize materials that achieve not only safe and effective hemostasis, but also have anti-infection and immunoregulation properties for the development of further hemostatic products.