Abstract Diseases caused by microorganisms have significantly impacted public health. Metal–organic frameworks (MOFs) and MOF-based materials with unique physical and chemical properties have shown promise as candidates for potent antimicrobial agents. In this review, the structural characteristics of MOFs that are demonstrated to be the main structural determinants in microorganism inactivation are discussed, with a particular focus on the type(s) of metal clusters, organic ligands, nanoparticles, and pores employed. A comprehensive overview of antimicrobial applications of MOFs and MOF-based composites on wound dressings, nano-pharmaceuticals, protective materials, antimicrobial surfaces, food preservation, and environmental decontamination will be presented in terms of these four structural elements. Last but not least, the future prospects of MOFs in antimicrobial applications as well as potential opportunities and challenges, are also elaborated.