The invasion of bacteria and inflammation impeded infected wounds heal. Here, a hyaluronan-based scaffold (HAG-g-C) was designed by cross-linking with gallic acid-modified gelatin to provide a protein microenvironment and decorated with cathelicidin-BF (CBF), a natural antimicrobial peptide, to remove bacterial infections and reverse the inflammatory environment. In vitro, HAG-g-C presented an antibacterial effect on Staphylococcus aureus and Escherichia coli. Meanwhile, it could drive the phenotypic switch of macrophage from M1 to M2 to accelerate tissue remodeling. In a mouse model of S. aureus-infected total skin defects, HAG-g-C inhibited the process of infection at the beginning of the wound and then regulated the M1 macrophage transformed to M2 phenotype on day 12. In addition, HAG-g-C induced collagen deposition, and reduced the expression of TNF-α, thereby significantly accelerating the reconstruction of infected wounds.