Objective: to determine the effect of nano-hydroxyapatite and different bioactive remineralizing agent in the treatment of loss of enamel minerals. Material &Methods: Initial enamel lesions were prepared in human enamel with an acid etching, then three remineralizing agents were applied on labial surface; nano-hydroxyapatite, Casein phospho-peptide amorphous calcium phosphate and Sodium Fluoride. While artificial saliva was applied on control specimens. Surface microhardness measurements baseline were calculated, and before/after demineralization was and digital 3D Profilometer was scanned. The data were collected ANOVA test was used followed by Tukey's post-hoc to compare between different variables and the significance level was set at P ≤ 0.05. Results: nano-hydroxyapatite group showed no significant difference mean hardness with CPP-ACP nanoparticle group while there is a significant difference between other remineralizing material. Nanohydroxyapatite was significantly greater than other material. Conclusion: Nano-hydroxyapatite has the potential to remineralize initial enamel lesions. Nano-hydroxyapatite and CPP-ACP are bioactive remineralizing agent that improve loss of enamel minerals. Nano-hydroxyapatite may be optimal for remineralization of early enamel caries.