Background. This systematic review aimed to evaluate the available scientific evidence concerning the effects of topical fluoride treatment on the bond strength of pit and fissure sealants. Prevention of dental caries is one of the crucial issues in pediatric dentistry. Pit and fissure sealant and fluoride therapies are two caries prevention procedures that may be performed in one session. However, fluoride therapy may affect the bond strength of pit and fissure sealants. Methods. An electronic search for in vitro studies published in English and Persian on topical fluoride therapy and the bond strength of pit and fissure sealants was performed via PubMed/ Medline, Web of Science, Google Scholar, Embase, and Scopus databases until May 2022. The articles were independently reviewed for quality by two reviewers. Textual data were analyzed manually, and the bond strength of sealants placed after fluoride application was compared with control groups. Results. A total of 8482 articles were initially identified and reviewed by two independent reviewers, and 13 were selected for full-text evaluation. Finally, six articles were included in the systematic review. A total of 250 teeth were studied, 148 of which were in the case group (fluoride group) and 102 in the control group. Tensile and shear bond strengths were compared between groups in the studies. Conclusion. In the studies in which the tooth surfaces were washed after applying fluoride, there was no change in the fissure sealant bond strength. However, in studies in which fluoride was not washed, the bond strength decreased significantly, independent of the fluoride type.