Resin-dentin bond degradation is a major cause of restoration failures. The major aim of the current study was to evaluate the impact of a remineralization medium on collagen matrices of hybrid layers of three different ad- hesive resins using nanotechnology methods. Coronal dentin surfaces were prepared from freshly extracted premo- lars and bonded to composite resin using three adhesive resins (FluoroBond II, Xeno-III-Bond, and iBond). From each tooth, two central slabs were selected for the study. The slabs used as controls were immersed in a simulated body fluid (SBF). The experimental slabs were immersed in a Portland cement-based remineralization medium that con- tained two biomimetic analogs (biomineralization medium (BRM)). Eight slabs per group were retrieved after 1, 2, 3, and 4 months, respectively and immersed in Rhodamine B for 24 h. Confocal laser scanning microscopy was used to evaluate the permeability of hybrid layers to Rhodamine B. Data were analyzed by analysis of variance (ANOVA) and Tukey's honest significant difference (HSD) tests. After four months, all BRM specimens exhibited a significantly smaller fluorescent area than SBF specimens, indicating a remineralization of the hybrid layer (P≤0.05). A clinically applicable biomimetic remineralization delivery system could potentially slow down bond degradation.