New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug -resistant bacteria and bacterial biofilms. This work reports the facile synthesis of antimicrobial dynamic cova-lent nano-networks (aDCNs) composing antibiotics bearing multiple primary amines, polyphenols, and a cross -linker acylphenylboronic acid. Mechanistically, the iminoboronate bond drives the formation of aDCNs, facili-tates their stability, and renders them highly responsive to stimuli, such as low pH and high H2O2 levels. Besides, the representative A1B1C1 networks, composed of polymyxin B1(A1), 2-formylphenylboronic acid (B1), and quercetin (C1), inhibit biofilm formation of drug-resistant Escherichia coli , eliminate the mature biofilms, alle-viate macrophage inflammation, and minimize the side effects of free polymyxins. Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 networks are also observed in a peritoneal infection model. The facile synthesis, excellent antimicrobial performance, and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.