Herein, a novel microfibrillated cellulose (MFC) reinforced natural polymer-based sponge composed of carboxymethyl chitosan (CMC) and oxidized starch (OS) with hemostatic, repairing-promoting, and antimicrobial performances was fabricated for chronic wound repair. When the content of MFC reached 1.2 wt%, the prepared sponge exhibited ultra-fast water or blood-trigged shape recovery property within 3 s. Moreover, sponge was functionally modified with silver nanoparticles (AgNPs) and recombinant humanized collagen type III (rhCol III). The AgNPs and rhCol III loaded sponge (A-Ag/III) could effectively kill a broad spectrum of pathogenic microbes, promote the proliferation and migration of L929 cells in vitro. Due to their erythrocyte-aggregating ability and positive-charge feature of CMC, the A-Ag/III displayed rapid hemostasis ability. Furthermore, the in vivo animal experiment demonstrated the A-Ag/III could promote wound repair by inhibiting inflammation, promoting angiogenesis, and cell proliferation. •A novel hemostatic MFC reinforced multifunctional sponge was developed.•The prepared sponges displayed superfast water/blood-trigged shape recovery property.•The prepared sponges showed a promoting effect on diabetic wound healing.