AIM: Effect of nanoparticles (NPs) loaded methylene blue (MB) mediated photodynamic therapy (PDT) on caries-affected dentin (CAD) against S.mutans, smear layer (SL) elimination, and shear bond strength (SBS) of single bottle 7th generation adhesive. METHODOLOGY: Sixty human molars with carious lesions were selected. Samples were randomly allocated into four groups, based on the disinfection regime (n = 11) Group 1-(CHX), Group 2-(MB-PDT), Group 3-(MB-CNPs-PDT), and Group 4-(MB-TiONPs-PDT). Following disinfection S.mutans' survival rate was assessed using the pour plate method. Five specimens from each disinfection group were subjected to SL removal assessment using a scanning electron microscope (SEM). Bonding of 7th generation adhesive and composite restoration was performed on ten samples from each group. Artificial aging of the bonded samples was performed followed by SBS and failure mode analysis using a universal testing machine and stereomicroscope respectively. One-way analysis of variance (ANOVA) and Tukey post hoc test were used to analyze the data. RESULTS: Group 3 (MB-CNPs-PDT) treated CAD surface unveiled the lowest survival rate (0.12 ± 0.02 CFU/mL) of tested bacteria, maximum SL removal (1.21 ± 0.35), and highest bond strength (13.42 ± 1.05). However, Group 1 (CHX) treated specimens displayed the highest survival rate (0.53 ± 0.11 CFU/mL) with the lowest SL removal (2.24 ± 0.30) and SBS (8.88 ± 0.73 MPa). CONCLUSION: MB-CNPs-PDT appears to be a suitable alternative to CHX for CAD disinfection as it displayed better antibacterial efficacy, SL removal, and SBS with 7th generation single bottle adhesive.