Objectives: Investigate the efficacy of biomimetic self-assembling peptide (P11-4) on enamel remineralization compared to casein phosphopeptide amorphous calcium phosphate (CPP-ACPF) and fluoride based delivery systems. Methods: Artificial enamel lesions were created on the buccal surfaces of 40 extracted human molars. Specimens were randomly assigned to 4 groups (n=10) according to the remineralizing agent used: G1- (Control, artificial saliva), G2- (Fluoride varnish), G3- (CPP-ACPF varnish), G4- (Self-assembling peptide agent). All products were applied according to the manufacturer’s instructions and specimens were stored in a daily renewed artificial saliva for 4 weeks. Surface microhardness (SMH) was assessed at baseline, after demineralization, after 1 week and 4 weeks storage. SMH values were analyzed using ANOVA and Tukey's post-hoc test. Results: Self-assembling peptide showed the highest statistically significant mean SMH followed by fluoride and CPP-ACPF while the lowest mean SMH was found in artificial saliva. However, no statistically significant difference was found between fluoride and CPP-ACPF. Higher statistically significant mean SMH was found after 4 weeks compared to 1 week remineralization in all groups. Conclusions: Self-assembling peptide confers the highest remineralizing efficacy compared to fluoride and CPP-ACPF; showing a promising, non-invasive regeneration potential. Also, extended period of time helped to attain more benefits from the remineralizing regimens applied. Clinical significance: The biomimetic self-assembling peptide technology is a paradigm for dental hard tissue engineering. With its capability to regenerate rather than repair carious lesions, it replaces and avoids invasive, lengthy therapies. Thus, it’s recommended for the treatment of non-cavitated caries lesions.