OBJECTIVE The aim of this study is to evaluate the influence of the antimicrobial photodynamic therapy with phycocyanin and toluidine blue on the bond strength of resin composite to the sound dentin. METHODS The samples include 120 tooth blocks taken from 60 human extracted sound third molar teeth. They were randomly divided into 12 groups and disinfected with two different photosensitizers (Phycocyanin and Toluidine blue) activated by 635 nm diode laser for aPDT procedure. Then two different protocols (total-etch and self-etch) of universal adhesive system (G-Premio BOND, GC Dental Products CORP. Japan) were applied. The samples then filled with resin composite (Gradia® Direct, GC Dental Products CORP. Japan). After 10000 cycles of thermocycling, all samples were subjected to the micro shear bond strength (μSBS) test using a universal testing machine (1 mm/min). The data were analyzed with One Way ANOVA. RESULTS The effect of aPDT using both photosensitizers (phycocyanin and toluidine blue O) on the bonding strength to dentin was not significant (P>0.05). However, the bonding strength of total etch groups was reduced significantly (P<0.05) after aPDT using both photosensitizers. Phycocyanin self-etch group showed the greatest bonding strength (19.48 ± 3.89 MPa) in comparison to other aPDT groups. No significant reduction after thermocycling in dentin bond strength was observed in all groups (P>0.05), with exception of control total etch groups, which showed significant difference (P<0.05). CONCLUSIONS aPDT using toluidine blue O and phycocyanin has no adverse effect on bonding to sound dentin when using universal adhesive in self-etch protocol. CONCLUSIONS Phycocyanin is more recommended to be used in aPDT in comparison to toluidine blue as a natural photosensitizer.