Introduction: Patients seeking orthodontic treatment are mainly targeting improving their esthetic, but they are faced with an un favorable side effect of fixed orthodontic treatment, which is enamel demineralization manifested as white spot lesions (WSLs). As a result, it's critical to alter caries risk factors and focus on therapeutic options that emphasize remineralization of lesions. Aim: The purpose of this study was to assess the clinical effect of self-assembling peptides and amorphous calcium phosphate varnish on the treatment of post orthodontic enamel WSLs. Materials and methods. In this prospective single-blinded randomized clinical investigation, a total of 40 patients' teeth (10 per group) were enrolled in four groups; first the control group, two remineralizing analogue groups; Self-assembling peptide P11-4 group (Curodont ™ Repair /Regenamel®), and Amorphous Calcium Phosphate varnish (Enamel Pro® Varnish 5% Sodium Fluoride Premier Dental). The combination of the two analogues were used to form the fourth group; through combining Self-assembling peptide containing a considerable quantity of calcium phosphate and fluoride ions. WSLs were evaluated using Vita Easy® Shade spectrophotometer (Vita Zahnfabrik, Germany) to calculate (∆E) of shade changes, immediately after de-bonding of the orthodontic brackets. Follow ups were done after one, three, and six months. Results: WSLs recovery was significantly better in the combination group followed by the s combine Self-assembling peptide group, than the control group, which had the lowest remineralization levels. Conclusion: Combining organic and inorganic remineralizing analogues showing the highest remineralizing potential reflected by the increase in Vita Easy® Shade readings.