In the wake of continual foodborne disease outbreaks in recent years, it is critical to focus on strategies that protect public health and reduce the incidence of foodborne pathogens and spoilage microorganisms. Currently, there are limitations associated with conventional microbial control methods, such as the use of chemical preservatives and heat treatments. For example, such conventional treatments adversely impact the sensorial properties of food, resulting in undesirable organoleptic characteristics. Moreover, the growing consumer advocacy for safe and healthy food products, and the resultant paradigm shift toward clean labels, have caused an increased interest in natural and effective antimicrobial alternatives. For instance, natural antimicrobial elements synthesized by lactic acid bacteria (LAB) are generally inhibitory to pathogens and significantly impede the action of food spoilage organisms. Bacteriocins and other LAB metabolites have been commercially exploited for their antimicrobial properties and used in many applications in the dairy industry to prevent the growth of undesirable microorganisms. In this review, we summarized the natural antimicrobial compounds produced by LAB, with a specific focus on the mechanisms of action and applications for microbial food spoilage prevention and disease control. In addition, we provide support in the review for our recommendation for the application of LAB as a potential alternative antimicrobial strategy for addressing the challenges posed by antibiotic resistance among pathogens.