Background: Fluoride varnish with therapeutic tricalcium phosphate formulas such as Clinpro™ varnish has shown greater tendency in treating white spot lesions (WSLs) by inhibiting the progression of initial enamel lesions through the mineral exchange. The self-assembling peptide SAP₁₁-4 (Curodont Repair, CDR) works on a different scale in treating WSLs by mimicking the enamel matrix and aiming to guided enamel regeneration. Aim: To quantitatively and qualitatively compare the effectiveness of the SAP₁₁-4 vs tricalcium posphate fluoride (TCPF) 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 I) or SAP₁₁-4 (group II). Lesions were assessed at pretreatment, 3, and 6 months posttreatment quantitatively per laser fluorescence DIAGNOdent pen and qualitatively through the International Caries Detection and Assessment System (ICDAS) II. Results: The result of the current study revealed a significant quantitative and qualitative increase in remineralization of WSLs in both groups and over time intervals. However, the WSL recovery was significantly better in the self-assembling peptide group, reflecting an excellent remineralization potential of the WSLs 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 remineralizing agents can limit unnecessary tissue loss, further caries progression, and consequently prevent further harm to the patients.