Designing expandable sponges with biodegradability and effective antibacterial properties are the urgent challenge for incompressible hemorrhage and wound healing. In the present investigation, based on quaternized gelatin (QG) and oxidized dextran (OD), a series of expandable sponges (ODQG) with high-water absorption capacity and robust mechanical properties were prepared. ODQG had good biodegradability in vitro and in vivo, and had inherent antibacterial activity (90% for E. coli and 99.74% for S. aureus). Due to the synergy effect of electrostatic interaction and blood concentration, ODQG could effectively attract and activate red blood cells/platelets and accelerate the coagulation process. Therefore, ODQG showed better hemostatic performance than Kuaikang® gelatin sponges and gauzes in incompressible hemorrhage model. Furthermore, ODQG could regulate inflammatory factor (TNF-α) and cytokines (TGF-β, VEGF), and greatly promote wound healing process. The biodegradable sponges with excellent antibacterial properties might have potential application prospect for incompressible hemostasis and wound healing in the future.