BackgroundThis study aimed to evaluate the impact of photodynamic therapy (PDT) using two photosensitizers, methylene blue and indocyanine green, on the microtensile bond strength of a universal adhesive to caries-affected dentin. MethodsThe occlusal enamel of 60 third molars was cut to expose the inner one-third of the dentin. Artificial caries were induced through a pH cycling process. The samples were divided into three groups: M (Methylene blue+ diode laser), I (Indocyanine green agents+ diode laser irradiation), and control. Each group was further divided into two subgroups according to the adhesive protocol (self-etch, total-etch). After restoring with Gradia composite resin, teeth were sectioned and exposed to 5000 thermal cycles. Microtensile bond strength was measured using a universal testing machine. The data were subjected to two- and one-way ANOVA and paired comparisons were performed by the Tamhane and Tukey tests. ResultsThe study found significant effects of the photosensitizer, etching pattern, and their interactions on the microtensile bond strength of composite resin to caries-affected dentin (P < 0.001). In the self-etching mode, PDT with indocyanine green exhibited significantly higher bond strength values compared to PDT with methylene blue (P = 0.001) and the control groups (P < 0.001). However, no significant differences were observed in the total-etch mode. (P = 0.54). ConclusionsThe etching mode played a more significant role in the bond strength when using the universal adhesive alongside PDT with methylene blue and indocyanine green. Employing two photosensitizers in PDT during the self-etch mode significantly increased the bond strength values.