AIMTo investigate the effect of different cavity disinfectants, Phycocyanin (PC), Ocimum Sanctum (OS), and Ti Sapphire Laser, on the bond integrity and microleakage of resin restorations. Material and method60 human mandibular molars were extracted and prepared based on ICDAS scores of 4 and 5. To obtain the CAD surface, a visual examination was supported by tactile sensation and a dye for caries detection. Samples were randomly allocated into 4 groups based on cavity disinfectants applied (n = 15). Group 1: Specimens disinfected with CHX, Group 2: Specimens disinfected with Ti sapphire laser, Group 3: Specimens disinfected with Phycocyanin activated by Photodynamic therapy, and Group 4: Specimens disinfected with OS. Following the disinfection of the CAD surfaces, composite bulk-fill restorative material was bonded to each specimen and all samples were subjected to thermocycling. Ten samples from each group underwent SBS testing performed on a universal testing machine. Five samples were subjected to a microleakage analysis. ResultThe maximum microleakage scores were displayed by Group 3: PC (0.521 nm) treated specimens. Whereas, and minimum microleakage was exhibited by Group 4: OS (0.471 nm). Group 4: OS (23.06±0.21 MPa) treated group displayed the maximum bond scores of resin adhesive to the CAD surface. However, Group 3: PC (21.67±0.24 MPa) treated specimens exhibited the lowest bond scores. Failure mode analysis revealed that among all the investigated groups the predominant type of failure was cohesive failure i.e., Group 1 (80%), Group 2 (80%), Group 3 (70%), and Group 4 (90%). ConclusionOcimum Sanctum, Phycocyanin activated by Photodynamic therapy, and Ti-sapphire laser for disinfection of caries-affected dentin have shown promise in terms of improved bond strength and reduced microleakage