This paper aims to provide a systematic review of the caries-prevention effect of probiotics in human. The hypothesis was that the administration of probiotic strains might play a role in caries lesion prevention and in the control of caries-related risk factors. The main relevant databases (Medline, Embase) were searched. Quality of the Randomized Clinical Trials (RCTs) was classified using the "Consolidated Standards of Reporting Trials" (CONSORT) checklist and the Impact Factor (IF) value of each journal was recorded. Sixty-six papers were identified, and 23 fulfilled the inclusion criteria. Only three studies had caries lesion development as outcome, all the others reported caries risk factors as interim evaluation. Using the CONSORT Score, the papers were coded as 4 excellent, 9 good and 10 poor. The mean IF value recorded was 1.438. Probiotics may play a role as antagonistic agent on mutans streptococci (MS), acidogenic/aciduric bacteria that contributes to the caries process. In two-thirds of the selected papers, probiotics have demonstrated the capacity to reduce MS counts in saliva and/or plaque in short-term. The effect of probiotics on the development of caries lesion seems encouraging, but to date, RCTs on this topic are insufficient to provide scientific clinical evidence.