Background: Disinfection of the prepared cavity can be a crucial step in the longevity of restorations. The objective of this study was to compare the antimicrobial action (AMA) of silver diamine fluoride?potassium iodide combination (SDF?KI) with 2% chlorhexidine gluconate (CHX) and to compare the alteration in bond strength and microleakage while using SDF?KI and CHX as cavity cleansers in resin?modified glass ionomer cement (RMGIC) restorations. Materials and Methods: Samples were grouped as follows: Group 1: Polyacrylic acid (PAA), Group 2: CHX, Group 3: SDF?KI, and Group 4: Distilled water (CTRL). AMA was assessed by measuring the zone of inhibition of the above?mentioned materials by dispensing them into the punch hole prepared on agar plates with an inoculum of Streptococcus mutans. For assessing the effect of the cavity cleansers on the bond strength of RMGIC, they were applied to the dentinal samples prepared from freshly extracted noncarious molars. After the surface was treated, cylindrical restoration of RMGIC was placed and allowed to set. The shear bond strength was then evaluated using a universal testing machine. Rhodamine?B dye penetration was viewed under a fluorescent microscope to evaluate the microleakage of RMGIC following surface treatment of the standardized cavities prepared on the cervical third of freshly extracted noncarious premolars. Results: SDF?KI (34 ± 0.8 mm) showed potent AMA followed by CHX (23.9 ± 0.7 mm) and PAA (12.7 ± 0.8 mm). SDF?KI showed a drastic increase in the bond strength when compared to the PAA, CHX, and CTRL groups. Although the application of SDF?KI showed the least microleakage among all the groups, it was not statistically significant. Conclusion: The application of SDF?KI and CHX is useful against S. mutans in an in vitro study. Although SDF?KI group showed the least microleakage among the groups, it was not statistically significant. SDF?KI application has shown a drastic increase in the bond strength of RMGIC although further research is required for the suitable reasoning of the phenomenon. Keywords: Antimicrobial action; bond strength; chlorhexidine gluconate; microleakage; potassium iodide; silver diamine fluoride