Significance This paper reports an exciting breakthrough in dynamic biomaterials design mimicking the reversible interlocking and remoldable structure of extracellular matrix (ECM). Specifically, we realize a nature-derived molecular recognition event (i.e., the antibiotic glycopeptide vancomycin [Van] and the dipeptide d -Ala- d -Ala [AA] receptor–ligand interaction) as a reversible strategy for fabrication of dynamic biointerface and 3D ECM mimics. We believe that the specific but reversible Van–AA molecular recognition would be a strategy for dynamic biomaterial fabrication, and that the easy-handling merit, ECM-like remoldability, and inherent antibacterial activity will bring insights to biomaterial scaffold design in tissue engineering and regenerative medicine.