<p>Lactic acid bacteria (LAB) are extensively utilized in the food industry to improve nutritional content, sensory attributes, and shelf life of various food products through the synergistic action of several antimicrobial metabolites and ecological processes. The synthesis of organic acids lowers the pH of the food matrix, destabilizing microbial membranes and rendering them vulnerable to antimicrobial agents such as bacteriocin, hydrogen peroxide, diacetyl, peptides, and fatty acids. These create an environment that is inhospitable to foodborne pathogens and spoilage microorganisms, which are amplified by the ability of LAB to rapidly colonize diverse ecological niches through efficient competition for nutrients and space. Despite their promising applications, challenges remain in optimizing LAB-based preservation systems for large-scale food production, including strain variability, stability concerns during storage, and regulatory obstacles. The application of LAB-derived secondary metabolites in food preservation, particularly biosynthesis, underlying action mechanisms, inhibitory factors, and impacts on food safety, quality, and stability, was eloquently explained in detail in this review paper. These secondary metabolites have also been employed with other bioactive agents and processing technologies as a synergistic approach to control food spoilage pathogens. Moreover, the challenges and limitations associated with their industrial adoption, synergistic application with emerging food processing technologies, and future prospects in the food industry have also been discussed. Harnessing the full potential of LAB in food preservation presents promising opportunities for developing innovative and sustainable substitutes for traditional chemical preservatives, which corresponds with the increasing consumer preference for safer, clean-label, and eco-friendly food products.</p>