Introduction: White spot lesions are an undesired side effect of fixed orthodontic treatment. The objective of this research was to develop an antibacterial resin-modified glass ionomer cement (RMGIC) containing nanoparticles of silver (NAg) for prevention of white spot lesions. Methods: NAg was incorporated into a commercial RMGIC. The NAg-enhanced cement was compared with the unaltered RMGIC and with a commercially available composite that does not release fluoride. The experimental and control products were used to bond brackets to 80 extracted maxillary first premolars. Enamel shear bond strength and the adhesive remnant index scores were determined. A dental plaque microcosm biofilm model with human saliva as the inoculum was used to investigate biofilm viability. Bacteria on the sample surface and bacteria in the culture medium away from the sample surface were tested for metabolic activity, colony-forming units, and lactic acid production. Results: Adding NAg to RMGIC and aging in water for 30 days did not adversely affect the shear bond strength compared with the commercial RMGIC control (P > 0.1). The RMGIC with 0.1% NAg achieved the greatest reductions in colony-forming units, metabolic activity, and lactic acid production. The RMGIC with 0.1% NAg inhibited not only the bacteria on the surface, but also the bacteria away from the surface in the culture medium. Incorporation of NAg into RMGIC greatly reduced biofilm activity. Conclusions: This novel RMGIC reduced biofilm formation and plaque buildup and could inhibit white spot lesions around brackets. The method of using NAg may apply in a wide range of dental adhesives, cements, sealants, and composites to inhibit biofilm and caries.