Background: Fluoride varnish with therapeutic tricalcium phosphate formulas(TCPF) such as Clinpro varnish has shown the greater tendency in treating white spot lesions (WSLs) by inhibiting the progression of initial enamel lesions through the mineral exchange. While the Self-Assembling Peptide SAP11-4 works on a different scale in treating WSLs by mimicking the enamel matrix and aiming to guided enamel regeneration. Aim: To compare quantitatively the effectiveness of the SAP11-4 (Curodont Repair, Credentis) versus TCPF (Clinpro varnish 3M ESPE) in remineralization of WSLs in young permanent teeth. Materials and methods: Nine healthy patients were enrolled in this study. The trial was performed on 40 young permanent teeth in the initial demineralization stage. Teeth were randomly assigned to receive either TCPF (Group A) or SAP11-4 (group B). Lesions were assessed at pretreatment, 3 and 6 months post treatment quantitatively by laser fluorescence DIAGNOdent pen. Results: The results revealed a significant increase in remineralization of WSLs in both groups and over time intervals. However, the WSL recovery was significantly better in the selfassembling peptide group, reflecting an excellent remineralization potential of the white spot lesions by the SAP11-4 compared to TCPF varnish. Conclusion: Both TCPF and SAP11-4 were effective in treating WSLs. However, the success of guided enamel regeneration by the SAP11-4 through the biomineralization has proven superiority of this material compared to TCPF. Clinical significance: Early detection of WSLs and minimal intervention through remineralising agents can limit unnecessary tissue loss, further caries progression and consequently prevent further harm to the patients. Keywords: White spot lesion, self-assembling peptide, tricalcium phosphate fluoride varnish, enamel regeneration, remineralization.