<p>The rapid development of antimicrobial resistance (AMR) has increased the quest of specific alternatives to the traditional antibiotics. Antimicrobial peptides that are ribosomally synthesized by bacteria under the name bacteria bacteriocins have received a lot of focus as precision antimicrobials because of their narrow spectrum activity, high potency, and lower probability of resistance development. The <i>Lactobacillus</i> species are of special interest among bacteriocin-producing microorganisms due to the lengthy record of safe application and its probiotic features and prominence in the human oral microbiome. The development of genomics and bioinformatics has transformed the discovery, classification, and functional characterization of <i>Lactobacillus</i>-derived bacteriocins to allow the identification of novel peptides and biosynthetic gene clusters with therapeutic potential. This review elasticities the genomic investigation of <i>Lactobacillus</i> bacteriocins such as genome mining techniques, regulatory measures, and structure function interactions. Moreover, it also draws attention to the new oral health uses, including dental caries, periodontal disease, and oral candidiasis prevention and management. Through the combination of genomic knowledge and translational studies, <i>Lactobacillus</i> bacteriocins are potential next-generation antimicrobials to the specific oral healthcare.</p> Graphical abstract <p></p>