Medical dressings, as a cover for wounds, can replace damaged skin in the wound healing process to play a temporary barrier role, avoid or control wound infection, and provide a favorable environment for wound healing. Therefore, there is an urgent need for medical antimicrobial dressings for the treatment of chronic wounds. Although traditional polyurethane foam has been widely used in medical dressings, conventional polyurethane foams are primarily prepared using nonbiocompatible isocyanate-based compounds, which are potentially hazardous for both operators and applications in the medical field. Here, we propose nonisocyanate polyurethane foams naturally derived from lignin by enzymatic lignin alkylation, cyclic carbonation modification, and polymerization with diamine and the addition of a blowing agent. Silver nanoparticle solution was added during foaming to confer antimicrobial properties. This lignin-based nonisocyanate polyurethane/silver composite foam (named NIPU foam-silver) using a green synthesis method has good mechanical properties, which can be used to manufacture polyurethane/silver foams, and thermal and antimicrobial properties. Notably, NIPU foam-Ag showed more than 95% bactericidal efficacy against both Escherichia coli and Staphylococcus aureus within 4 h. Evaluation of in vitro wounds in mice showed that this antimicrobial composite foam rapidly promotes wound healing and repairs damaged tissue. This suggests that this biobased biodegradable antimicrobial foam has significant scope for clinical applications in wound management.