To evaluate the effectiveness of a calcium silicate/phosphate fluoridated tooth paste and a serum compared with a toothpaste containing hydroxyapatite on protecting the enamel after interproximal reduction against demineralization. 3 sets of eleven incisors were created. The teeth underwent interproximal enamel reduction (IER) of 0.5 mm. Each set was allocated to one of three groups: (1) Brushing without toothpaste (control group); (2) Vitis toothpaste + Remin Pro; (3) Regenerate toothpaste + Regenerate Serum. The agents were applied three times a day and specimens subjected to demineralization cycles for 30 days. The weight percentages of calcium (Ca) and phosphorous (P) were quantified by X-ray microfluorescence spectroscopy. Surface microhardness measurements and electron scanning microscopy (SEM) observations were made. Ca data and the Ca/P ratio were significantly higher in Group 3 than the other groups (p < 0.017), while P was significantly lower in Group 3 (p < 0.017). No significant differences were found between Groups 1 and 2 (p > 0.017). Group 3 showed significantly higher microhardness values (p < 0.05) than Group 1. No significant differences were found for other comparisons between groups (p < 0.05). SEM images showed less demineralization in Group 3. The application of a calcium silicate/phosphate fluoridated tooth paste (Regenerate advance) and a dual serum (Regenerate advance enamel serum) protect the enamel with interproximal reduction against demineralization. Therefore, this treatment could be used to prevent the dissolution of hydroxyapatite after IER.