Covalent organic frameworks (COFs), as an emerging class of crystalline porous polymeric material, process large surface area, ordered pore structure, good biocompatibility, excellent chemical stability, and low toxicity, making it an excellent candidate for nanotherapeutics. In this article, the recent research progress of COFs was reviewed in the antibacterial field. We introduced the antibacterial potential of COF materials themselves, covering framework structures and pore chemistry. Moreover, the synergistic antibacterial effects of COF composites were discussed, which were formed by the combination of COF with other nanomaterials. In addition, the excellent performances of COFs as nanozymes were investigated in antibacterial applications. Currently, COF-based high-efficiency antibacterial agents face great challenges and prospects in practical applications. The review will provide new COF-based methods for resolving drug-resistant bacterial issues.