The incorporation of remineralizing additives into sealants has been considered as a feasible way to prevent caries by potential remineralization through ions release. Thus, this systematic review aimed to identify the remineralizing additives in resin-based sealants (RBS) and assess their performance. Search strategies were built to search four databases (PubMed, MEDLINE, Web of Science and Scopus). The last search was conducted in June 2020. The screening, data extraction and quality assessment were completed by two independent reviewers. From the 8052 screened studies, 275 full-text articles were assessed for eligibility. A total of 39 laboratory studies matched the inclusion criteria. The methodologies used to assess the remineralizing effect included microhardness tests, micro-computed tomography, polarized-light microscopy, ions analysis and pH measurements. Calcium phosphate (CaP), fluoride (F), boron nitride nanotubes (BNN), calcium silicate (CS) and hydroxyapatite (HAP) were incorporated into resin-based sealants in order to improve their remineralizing abilities. Out of the 39 studies, 32 studies focused on F as a remineralizing agent. Most of the studies confirmed the effectiveness of F and CaP on enamel remineralization. On the other hand, BNN and CS showed a small or insignificant effect on remineralization. However, most of the included studies focused on the short-term effects of these additives, as the peak of the ions release and concentration of these additives was seen during the first 24 h. Due to the lack of a standardized in vitro study protocol, a meta-analysis was not conducted. In conclusion, studies have confirmed the effectiveness of the incorporation of remineralizing agents into RBSs. However, the careful interpretation of these results is recommended due to the variations in the studies’ settings and assessments.