Objective: Tooth surface undergoes continuous remineralization and demineralization. The aim of this study was to compare the effect of Caseinphosphopeptide-amorphous calcium phosphate (CPPACP) paste and Fluoride gel on the microhardness of demineralized enamel lesions.Methods: Frothy eight specimens of premolar teeth were chosen and randomly divided to 4 groups of 12. After the initial measurement of micro-hardness the specimens were immersed in demineralizing solution for 4 day and then the measurements were recorded again. Two groups (GL and G3) were treated with Cpp-Acp and Fluoride gel respectively according to manufacturer’s instruction. Two other groups (G2 and G4) were treated with Cpp-Acp and fluoride gel every week for three months. After the treatments all specimens were taken into PH-cycling and the microhardness for each one were measured again. For data analysis, the Repeated Measures ANOVA test and the LSD tests were performed. In each group the percentage of micro-hardness recovery was measured.Results: Repeated Measures ANOVA and LED Test showed that the mean value of hardness was significantly decreased after demineralization in all groups (p=0.01). There was no significant difference in mean hardness value in groups (GL, G3) after treatment (p=0.1, p=0.12) In groups (G2, G4) the mean hardness value were significantly increased (p<0.0001, p=0.1). It is noticeable that the Cpp-Acp was significantly more efficient than the fluoride gel.Conclusion: CPP-APC paste and fluoride gel both increase the micro-hardness of enamel when administrated for long time and repeated application.