Aim: The study was conducted with the aim to compare the efficacy of sodium monofluorophosphate and nanohydroxyapatite-containing toothpaste in remineralizing artificial caries on extracted primary teeth using the Vickers surface microhardness test. Materials and methods: This experimental in vitro study was conducted on 30 freshly extracted primary teeth from individuals requiring extractions as part of their dental treatment. The lottery method was used to randomly divide the samples into two groups remineralization using nanohydroxyapatite (nano-HA) group (coded group I) and remineralization using the sodium monofluorophosphate group (group II). All the samples were subjected to a demineralization regimen using a demineralizing agent for 48 hours. Then all the samples were subjected to remineralizing regime using sodium fluoride (NaF) toothpaste (226 ppm) and nano-HA toothpaste for 28 days. Surface microhardness for remineralized samples was recorded using the Vickers microhardness test by utilizing a 25 gm load for a duration of 5 seconds. The results were statistically analyzed using the analysis of variance test and post hoc test at a 5% level of significance. Results: The baseline microhardness expressed as Vickers hardness number (VHN) for the nano-HA group (group I) was 341.73 ± 5.07; 256.54 ± 5.10 VHN after demineralization and 321.27 ± 6.48 VHN after remineralization, respectively. For the sodium monofluorophosphate group (group II), the microhardness value was found to be 365.56 ± 5.69 VHN at baseline, 275.65 ± 5.22 VHN after demineralization, and 313.10 ± 8.02 VHN postremineralization. Conclusion: Nanohydroxyapatite (nano-HA) causes remineralization and increases the microhardness of the tooth at the microstructural level. Therefore, it is a novel method to remineralize initial carious lesions. Clinical significance: Remineralization therapy is a contemporary approach for carious lesions in early detection and a noninvasive or minimally invasive treatment approach, which is crucial for the dental profession in shifting their therapeutic approach to a new paradigm. The present study showed that nano-HA toothpaste has the potential to remineralize the artificial carious lesion.