In this study, chitosan/alginic acid/zinc oxide (CHI/AA/ZnO) nanostructured hydrogel sponges were fabricated by incorporating ZnO nanoparticles (<100 nm) into polymer matrix to develop a new potential biomaterial for hemorrhage control. For this purpose, the crosslinked CHI/AA/ZnO nanostructured sponges were synthesized by freeze‐drying technique. Genipin was used as a crosslinker. The prepared chitosan‐based sponges were characterized by Fourier transform infrared spectroscopy, X‐ray diffraction, and scanning electron microscopy—energy‐dispersive spectroscopy analysis. The effects of ZnO content on the physicochemical characteristics of sponge‐like nanostructured hydrogels were evaluated by swelling ratio in two different pH values. Physical immobilization of dexamethasone as a model drug in hydrogel matrix resulted sustained release of drug more than 3 days. Antibacterial activity of hydrogel sponges was assessed against Staphylococcus aureus. The cytotoxicity and hemostatic efficacy of crosslinked CHI/AA/ZnO sponge like‐nanostructured hydrogels was evaluated in vitro and in vivo, respectively. The results of this study demonstrated that the prepared CHI/AA/ZnO nanostructured sponge had the potential to be an antibacterial topical hemostat. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47522.