Skin wound healing remains a key challenge owing to its vulnerability to pathogen infection, oxidative stress and persistent inflammatory response. Herein, a salen-manganese complex (EUK)-based nanozyme was designed to simultaneously circumvent these barriers. The nanozyme was prepared by the amidation reaction between degradable chito-oligosaccharide (COS) and EUK. Positive charged COS and metallic compounds (EUK) could allow the nanozyme (COS-EUK) synergistic antibacterial activity. Due to the protection and synergistic catalytic enhancement effect provided by COS, superoxide (SOD)- and catalase (CAT)-like capability of COS-EUK was significantly improved compared with EUK. The nanozyme could eradicate not only O2− but also the generated H2O2, further supplying O2 to promote fiber cell proliferation. Moreover, COS-EUK could prevent macrophages from transforming into classically activated macrophages (M1 phenotype), and endow them anti-inflammatory effects. COS-EUK can accelerate bacteria-infected skin wound healing. Thus, COS-EUK provides a promising strategy for bacteria-infected wound healing with great potential in clinical infection.