Self-assembling peptide has been recently introduced to promote hard tissue regeneration for treating early non-cavitated carious lesions. This study investigates the efficacy of biomimetic self-assembling peptide (P11-4) on enamel remineralization combined with CPP-ACPF or fluoride. Artificial enamel lesions were created on buccal surface of 60 specimens and were randomly assigned to six groups according to the remineralizing agent: G1-(Control, artificial saliva), G2-(Fluoride varnish), G3-(CPP-ACPF varnish), G4-(Self-assembling peptide), G5-(Self-assembling peptide+fluoride varnish), G6-(Self-assembling peptide+CPP-ACPF varnish). All products were applied according to manufacturer?s instructions and specimens were stored in a daily renewed artificial saliva. Surface microhardness (SMH) and scanning electron microscope (SEM) were assessed at baseline, after demineralization, 1 week and 4 weeks storage. SMH values were analyzed using ANOVA and Tukey?s post-hoc test. The highest statistically significant SMH values were found in G6 followed by G5, G4, G2 and G3 while the lowest values were found in G1. No statistically significant difference was found between G5 and G6. Also, no statistically significant difference was found between G2 and G3. SEM showed that G4, G5, G6 resulted in more pronounced remineralization, reversing the demineralized enamel fish scale pattern compared to G2 and G3 after 1 week and 4 week remineralization. Complementary effect was obtained after combining self-assembling peptide with CPP-ACPF or fluoride showing the highest remineralizing potential early after 1 week and even after 4 weeks compared to when each agent used alone. Added benefits can be obtained through combining self-assembling peptide with other remineralzing agents allowing faster and enhanced regeneration of non-cavitated caries lesions.