In recent years, antibiotic-conjugated nanoparticles have attracted great interest for use as antimicrobial agents. Unfortunately, most of antibiotic-conjugated nanocomposites are involved in a multi-step and time-consuming process. Herein, we developed a vancomycin-encapsulated ZIF-8 (VAN@ZIF-8) nanoparticles by a simple one-pot approach to combat bacteria. The prepared VAN@ZIF-8 nanoparticles have the capacity to recognize gram-positive bacteria because of the strong and specific five-hydrogen bond between the VAN and the D-alanyl-D-alanine dipeptide coming from gram-positive bacteria cell wall. Importantly, owing to the multivalent nanoparticle-bacterium interactions, the VAN-encapsulated ZIF-8 nanoparticles exhibit a higher antibacterial efficacy in gram-positive bacteria compared to the free VAN molecules. In addition, the VAN@ZIF-8 nanoparticles as photocatalysts also show a strong photoinactivation of the bacteria under light irradiation. The present study is of interest for opening up tremendous opportunities to make good use of ZIF-8 and other MOFs in applications to combat bacteria, because of their excellent antibacterial activity and facile preparation method. [GRAPHICS] .