Wound infection by multidrug-resistant bacteria seriously threatens human life. Chronic wounds, with necrosis, persistent inflammation, and covered by hypoxic tissue, seriously hinder anti-infection treatments. Herein, we have developed a multifunctional hydrogel dressing with antibacterial activity in the hypoxia environment to promote wound healing. The hydrogel comprises Cypate-conjugated antimicrobial peptides (AMP-Cypates), liposome-encapsulated perfluorodecalin, and recombinant type III collagen. AMP-Cypates exhibited outstanding antibacterial activity, jointly achieved through antimicrobial peptide (AMP) activity, photothermal therapy (PTT), and photodynamic therapy (PDT). The perfluorodecalin liposomes act as the oxygen carrier to mitigate wound hypoxia condition and enhance the efficacy of PDT. The recombinant type III collagen in the hydrogel further promoted the healing of the wounds together with the eradication of bacterial infection. Taken together, the hydrogel dressing provides a platform for integrating multiple antimicrobial mechanisms for the rapid removal of bacterial infection and the healing of chronic wounds.