OBJECTIVE: This systematic review aimed to evaluate the current evidence regarding the impact of postbiotics on dental caries, focusing on the effectiveness of postbiotic interventions in caries prevention, mechanisms of action, optimal dosages, and administration protocols. METHODS: A literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library. Eligible studies included randomized controlled trials, quasi-experimental, observational, and in vitro studies. The selection followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A qualitative synthesis was performed due to heterogeneity in study designs and outcomes. RESULTS: Twenty-one studies were included (18 in vitro and three randomized controlled trials). Postbiotics derived from various Lactobacillus species demonstrated inhibitory effects on Streptococcus mutans growth, biofilm formation, and virulence gene expression. Proposed mechanisms include direct antimicrobial activity, inhibition of bacterial adhesion, disruption of biofilm formation, modulation of immune responses, and pH buffering. After postbiotic interventions, human trials showed reduced salivary S. mutans counts and increased salivary pH. CONCLUSIONS: Postbiotics offer a promising novel approach to dental caries prevention by targeting cariogenic bacteria and modulating the oral microbiome through multiple mechanisms. Compared to probiotics, postbiotics present additional advantages, including enhanced safety, stability, and ease of incorporation into oral care products.