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Dental caries is a highly preventable and costly disease. Unfortunately, the current management strategies are inadequate at reducing the incidence and new minimally invasive strategies are needed. In this study, a systematic evaluation of specific light parameters and aqueous curcumin concentrations for antimicrobial photodynamic therapy (aPDT) was conducted. Aqueous solutions of curcumin were first prepared and evaluated for their light absorbance after applying different ~56 mW/cm² blue light treatments in a continuous application mode. Next, these same light treatments as well as different application modes were applied to the curcumin solutions and the molar absorptivity coefficient, reactive oxygen species (ROS) release, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) for Streptococcus mutans and the MIC and minimum fungicidal concentration (MFC) for Candida albicans were measured. After up to 1 min of light treatment, the molar absorptivity of curcumin when added to culture media was lower than that for water only; however, at higher energy levels, this difference was not apparent. There was a noted dependence on both ROS type and cariogenic microorganism species on the sensitivity to both blue light treatment and application mode. In conclusion, this study provides new information towards improving the agonistic potential of aPDT associated with curcumin against cariogenic microorganisms.