Introduction: The natural healing process for non-cavitated lesions is remineralization (Remineralization is considered the main natural process for noncavitated lesions healing). Fluoride is the main constituent of numerous remineralizing agents and casein phosphopeptides amorphous calcium phosphate fluoride (CPP-ACPF) have already proved their remineralizing potential. Regenerative biomimetic approaches in remineralization have been introduced in the market based on the use of self-assembly peptides (SAP) and already showed an effective remineralizing effect. Aim : To clarify the effect of combining fluoride or CPP-ACPF with SAP compared to the remineralizing potential of SAP on its own. Materials and Methods: Artificial enamel lesions were created on the buccal surfaces of 60 samples. Samples were randomly distributed into two equal groups (30 ones /each). Group (B0): received no biomimetic material, group (B1): biomimetic material was applied. Each group was further subdivided randomly into 3 subgroups of 10 specimens each according to the remineralizing material used; either (R0) artificial saliva, (R1) fluoride, or (R2) CPP-ACPF. Specimens of enamel were put through a pH-cycling model for 8 days. A Vickers microhardness tester was used in assessing surface hardness (SMH) before demineralization of the specimens as a baseline, after demineralization, after remineralization, and after pH cycling. The resulting values were analyzed using ANOVA. Results: The percentages of microhardness change were compared after remineralization and pH-cycling, in which, we found that regardless of remineralizing agents; group B1 showed a statistically significantly higher value than group B0. Regardless of biomimetic material, group R2 showed a statistically significantly highest mean percentage change. And when combined, group B1R2 had the statistically significant highest value of all groups. Conclusion: SAP showed superior remineralization potential in comparison to fluoride and CPP-ACPF-based remineralizing agents. SAP showed a synergistic effect when combined with both fluoride and CPP-ACPF. However. Its synergistic effect was superior with CPP-ACPF-based varnish.