Foodborne pathogens pose a major threat to human health, society, and economy. Contamination by pathogenic bacteria can cause foodborne diseases at any stage of the farm-to-table food supply chain. As drug resistance becoming an increasingly serious global issue, there is an urgent need to develop novel methods for controlling foodborne bacteria. Lysins are enzymatic proteins produced by most virulent phages that can degrade bacterial cell walls. These antibacterial proteins have attracted growing interest from researchers because of certain favorable characteristics, such as strong bactericidal activity, high host specificity, low tendency to induce drug resistance, and potential for engineering modification. This review summarizes the classification, structure, and antibacterial mechanisms of lysins, explores strategies to enhance their activity against gramnegative bacteria, highlights recent advances in their application for preventing and controlling foodborne pathogens, and provides perspectives on their future development and use. The insights presented herein aim to inform the design of novel strategies for combating drug-resistant foodborne pathogens.