Microorganisms induced wound infection and the accompanying excessive inflammatory response is the daunting problems in wound treatment. Due to the lack of corresponding biological functions, traditional wound dressings cannot effectively protect the wound and are prone to induce local infection, excessive inflammation, and vascular damage, resulting in prolonged unhealing. Here, a mussel-inspired strategy was adopted to prepare a multifunctional hydrogel created by H2O2/CuSO4-induced rapid polydopamine (PDA) deposition on carboxymethyl chitosan (CMC)/sodium alginate (Alg) based hydrogel, termed as CAC/PDA/Cu(H2O2). The prepared CAC/PDA/Cu(H2O2) hydrogel features excellent biocompatibility, adequate mechanical properties, and good degradability. Moreover, the CAC/PDA/Cu(H2O2) hydrogel can not only realize antibacterial, and anti-inflammatory effects, but also promote angiogenesis to accelerate wound healing in vitro thanks to the composite PDA/Cu(H2O2) coatings. Significantly, CAC/PDA/Cu(H2O2) hydrogel illustrates excellent therapeutic effects in Methicillin-resistant Staphylococcus aureus (MRSA) induced-rat infection models, which can efficiently eliminate MRSA, dramatically reduce inflammatory expression, promote angiogenesis, and ultimately shorten the wound healing time. CAC/PDA/Cu(H2O2) hydrogel exhibited the best wound healing rate on days 7 (80.63 ± 2.44 %), 11 (92.45 ± 2.26 %), and 14 (97.86 ± 0.66 %). Thus, the multifunctional hydrogel provides a facile and efficient approach to wound management and represents promising potential in the therapy for wound healing.Copyright © 2022. Published by Elsevier B.V.