Abstract Background: Early childhood caries is one of the most serious and high-priced oral health conditions among young children. With advancing dental sciences, the focus of dental caries treatment is shifted from restorative procedures to preventive measures, and a modality grabbing attention is probiotics. Probiotics exert their effects in many ways as chemical inhibition of pathogenic bacteria and stimulation of the immune response through the production of immunoglobulin A and many more. Objective: This systematic review aims to explore the efficacy and safety of probiotics in dental caries in preschool children. Methodology: The study was registered in the PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42020159058). The search was done for randomized control trials in electronic databases such as Cochrane, PubMed, ClinicalTrials.gov, Medline, and Embase. It has further included manual searches of journals, conference abstracts, and books. Three reviewers done the selection of the study as per the criteria and also did the risk of bias assessment independently and wherever required, a fourth reviewer resolved the discrepancy in case of disagreement. Results: The nine randomized control trials were included in the study, and the pooled analysis revealed probiotics as an effective intervention in preschool children with dental caries. Conclusion: The results about the efficacy of probiotics in the prevention of dental caries are very encouraging, though the level of evidence is still inadequate.