Bioactive materials that are capable of releasing remineralizing ions may be an interesting alternative treatment to prevent the development of carious lesions. The purpose of this study is to evaluate the effectiveness of the association of 45S5 with resin-modified glass ionomer cement (GIC-MR) for conservation and prevention of the progression of initial carious lesions in permanent molars. A total of 36 patients, aged 8 to 14 years, with at least two permanent molars homologous with ICDAS (International Caries Detection and Assessment System) 3 or 4 will be selected to participate in a clinical study of the split-mouth type. The DLF-T (Decayed, Lost and Filled Teeth index), ICDAS, BOP (Bleeding on probing), and VPI (Visible Plaque Index) will be analyzed. A complementary radiographic exam will be performed to assess the dentin underlying lesion. The selected teeth will be randomly assigned into two groups: GIC-MR and GIC-MR + 45S5. Parameters such as retention, the clinical performance of materials, and caries evolution will be evaluated into the two studied groups. Two calibrated evaluators will perform clinical, radiographic, and microscopic evaluations at one, six, 12, and 24 months of follow-up. The results obtained will be evaluated using a Chi-square test. The intention-to-treat protocol will be followed. The results of this study will help to assess the behavior of a bioactive glass ionomer in lesions with enamel microcavities. Innovative research projects, such as the one described here, are needed to determine whether new materials can be used as a treatment alternative.