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Background: There are investigations on multiple photosensitizers for modulation of caries-related biofilms using PDT. However, much controversy remains about recommended parameters mostly on the selection of an efficient photosensitizer., Objective: The study performed a systematic review to identify the answer to the following question: What photosensitizers present high bactericidal efficacy against cariogenic biofilms?, Methods: Systematic review with meta-analyses were carried out for English language articles from October to December 2019 (PRISMA standards) using MEDLINE, Scopus, Biomed Central, EMBASE, LILACS, and Web of Science. Information on study design, biofilm model, photosensitizer, light source, energy delivery, the incubation time for photosensitizer, and bacterial reduction outcomes were recorded. We performed two meta-analyses to compare bacterial reduction, data was expressed by (1) base 10 Logarithm values and (2) Log reduction RESULTS: After the eligibility criteria were applied (PEDro scale), the selected studies showed that toluidine Blue Ortho (TBO) and methylene blue (MBO) (5-min incubation time and 5-min irradiation) demonstrated better bacterial reduction outcomes. For the data expressed by Log TBO, MBO, curcumin, and Photogem® presented a significant bacterial decrease in comparison to the control (p = 0.042). For the data represented by Log reduction, the bacterial reduction toward S.mutans was not significant for any photosensitizer (p = 0.679)., Conclusion: The lack of methodological standardization among the studies still hinders the establishment of photosensitizer and bactericidal efficiency. TBO, MBO, curcumin, and photogem generate greater PDT-based bacterial reduction on caries-related bacteria.. Further clinical studies are necessary in order to obtain conclusive results., (Copyright © 2020. Published by Elsevier B.V.)