Background: the most prevalent chronic condition in the world is caries; the revolution in minimally invasive dentistry clarified the necessity for clinically effective methods to allow remineralization of newly formed enamel caries, and Nanotechnology provides new approaches. Nano-sized ZnO In addition to the individualized antifungal and antibacterial properties, it has been used in fluoride precipitation from aqueous solutions; it acts as an adsorbent to remove F ions. The study aimed to test the effect of applying Zinc Oxide NP with Sodium Fluoride solution on the microhardness of artificially induced dental caries on the enamel surface compared to Sodium Fluoride alone. Materials and methods: thirteen upper first premolars extracted for orthodontic treatment were used.results: the nanoparticles increase the surface remineralization more than sodium fluoride alone and have more excellent microhardness scores. Conclusion: Using zinc Oxide nanoparticles with sodium fluoride is better than using sodium fluoride alone. Keywords: Dental caries, Noninvasive dentistry, Nanoparticles, Zinc Oxide Nanoparticles, Reminerlization.