Background: Despite the fact that fluoride-based remineralization technologies have dominated preventive dentistry for the past century, but new and innovative nanomaterials approaches are transforming the industry. A variety of unique nanomaterials are now easily available to assist remineralization of dental enamel surface. Objective: investigate the effect of indium oxide nanoparticles application in comparison to de-ionized water and sodium fluoride on human tooth enamel by assessing the morphological changes in enamel ultra-structure. Using a field emission scanning electron microscope, x-ray diffraction, and ultraviolet visible absorption to evaluate the physical characteristics of indium oxide nanoparticles created by laser ablation in liquid. Method: Teeth samples were seventy-two divided randomly into two phases; each phase consists of study and treated groups with indium oxide nanoparticles, control positive treated with sodium fluoride, and control negative with deionized water. Each group was consisted of twelve teeth, from each group two teeth for scanning electron microscopy and the rests were for energy dispersion spectroscopy. Result: result showed change in chemical composition of dental enamel was recorded for both preventive and treatment groups after nanoparticles application and this was supported by energy dispersive spectroscopy and scanning electron microscope. Conclusion: Laser prepared indium oxide nanoparticles colloidal suspensions were found to be effective remineralizing agent to dental enamel and thus can be considered as an alternative to sodium fluoride mouth wash.