The prevention of bacterial infection and prompt wound repair are crucial considerations when local skin tissue is compromised by burns, cuts, or similar injuries. Porcine acellular dermal matrix (pADM) is a commonly employed biological material in wound repair due to its inherent natural properties. Nonetheless, the pADM's primary constituent, collagen fibers, lacks antimicrobial properties and is vulnerable to bacterial infection when used in the treatment of incompletely debrided wounds. Meanwhile, conventional antimicrobial agents primarily consist of chemical compounds that exhibit inadequate biocompatibility and biological hazards. This research endeavors to create an antimicrobial collagen scaffold dressing utilizing the Schiff base reaction through the incorporation of oxidized chitosan diquaternary (ODHTCC) salt into the pADM. Compared with the unmodified pADM, ODHTCC-pADM (OD-pA) still retained the three-stranded helical structure of natural collagen. At an ODHTCC cross-linker concentration of 4%, the thermal denaturation temperature of OD-pA was 85 °C. According to the enzymatic degradation resistance test in vitro, the degradation resistance of OD-pA to type I collagenase was significantly improved compared with that of the uncross-linked pADM. In addition, OD-pA exhibited good antibacterial properties, with inhibition rates of 95.6% and 99.9% for E. coli and Staphylococcus aureus, respectively, and a cytotoxicity level 1, meeting the in vitro requirements of national biomedical materials. In vivo experiments showed that the OD-pA scaffold could better promote wound healing and more effectively promote the positive expression of bFGF, PDGF and VEGF. In conclusion, OD-pA has struck a balance between antibacterial properties, chemical reaction properties and biocompatibility, ultimately achieving controllability, and has broad application prospects in the field of antibacterial biomedical materials.