Aim: This study was designed to evaluate and compare the re-mineralization potential of different biomimetic materials; self assembling peptide (P11-4), highly concentrated sodium fluoride agent and combination of fluoride, hydroxyapatite and xylitol paste on the white spot lesions. Materials and Methods: This study was conducted on 45 white spot lesions. Each white spot lesion was scored according to severity using the ICDAS II criteria, then assigned into three groups of 15 lesions each according to the re-mineralizing material used; Group A1: 15 lesions were treated with Self assembling peptide (P11-4) (curodont repair), Group A2: 15 lesions were treated with highly concentrated sodium fluoride agent (LunosĀ® Polierpaste Two in One), Group A3: 15 lesions were treated with fluoride, hydroxyapatite and xylitol paste (Remin Pro forte). Saliva pH was checked every month for three months using CRT buffer. Photographic records were taken before treatment and after treatment then after three months. Patients were recalled after 1 month, 2 months and 3 months of re- mineralizing agents' application. Data was presented as mean, median, standard deviation (SD). As most of the data was parametric, the differences between groups were evaluated by one way analysis of variance (ANOVA) test. This was followed by Tukey's post hoc test when ANOVA yielded positive results. The level of significance was set at P < 0.05. Results: the mean percentage change in ICDAS II scores improved for all the three re- mineralizing agents used as compared to baseline. No significant difference was noted at baseline (p=0.54). However, at 3 months the difference between groups was statistically significant, since most of the cases in Remin Pro group recorded score 1 (66.6%), while most of the cases in Curodont and Lunos 2 in 1 group scored 2 (53.3% and 80% respectively). Score 0 recorded (20%) for Remin Pro while (13.3%) scored for Curodont. On the other hand, Lunos polier paste recorded no 0 score. According to Saliva buffer results; as a comparison between the three groups, pH of group (A3: Remin Pro forte) showed higher increase followed by group (A1: Curodont repair) then group (A2: Lunos polierpaste 2 in 1). Conclusions: All the tested materials have varying re-mineralization potential through Remin Pro forte was the most efficient. Self assembling peptides (P11-4) seem to believe in resisting the acid challenge. All agents were clinically efficient in management of white spot lesions