Background: Dental caries is the most common disease in childhood and has an impact on general health status. The topical application of fluoride varnishes has been used for the prevention and control of dental caries due to their high fluoride content, adhesion capacity, and safety. Silver has a varied application in medicine as well as in dentistry due to its anticaries, antimicrobial, and antirheumatic potentials. The introduction of nanosilver fluoride (NSF) was made with advancements in technology to overcome the drawbacks of silver diamine fluoride (SDF). Aim: To compare and evaluate the microhardness and microleakage of NSF varnish and sodium fluoride (NaF) varnish. Materials and methods: An in vitro comparative experimental study was carried out between synthesized NSF and commercially available NaF, with 20 samples in each group. The specimens were sectioned and subjected to microhardness evaluation using Vickers microhardness testing and the dye penetration method to evaluate the microleakage. Results: The average microhardness was found to be 230.7218 VMH for NSF (group I), 198.9841 VMH for NaF (group II), and 91.6120 VMH for group III. These differences were statistically significant when compared with each other (p = 0.002). In 50% of the samples, no dye penetration was seen in the NSF group, compared to the NaF varnish group, where 75% of the samples exhibited penetration onto the varnish interface or the varnish and tooth interface. Conclusion: Nanosilver fluoride proves to be an effective alternative to commercially available topical fluoride agents such as NaF. It has greater microhardness and lower microleakage than NaF and the control teeth. Clinical significance: Nanosilver fluoride varnish can be used as a cost-effective alternative to NaF varnish and SDF. It can be applied with minimal training by healthcare workers or general practitioners.