ObjectivesThis study aimed to measure the distribution of silver ion (Ag+), mineral recovery, and nanohardness in carious lesions and comprehensively evaluate the degree of dentin restoration. MethodsSixty human teeth with root caries were randomly assigned to the control, silver diammine fluoride (SDF) [Safo], and SDF+Glass ionomer cement (GIC) treatment [Safo+Fuji] groups. Micro-computed tomography (micro-CT) was performed at five time points for each sample before/after treatment to evaluate mineral density within and around carious lesions. Three months following treatment, 12 samples were selected for synchrotron radiation X-ray fluorescence analysis to evaluate Ag+ distribution, while 15 samples were selected for nanoindentation. Data were analyzed using Dunnett's T3 test for micro-CT and Wilcoxon rank sum test with Bonferroni correction (p = 0.017) for nanoindentation. The correlation between hardness and mineral change was analyzed using the Spearman rank correlation coefficient. ResultsThe Safo and Safo+Fuji groups showed significantly higher mineral recovery rates than did the control group (p < 0.001). In the Safo group, Ag+ accumulated in the deeper layers rather than the superficial layer of caries. In the Safo+Fuji group, Ag+ was found evenly distributed throughout caries, with only a few Ag+ detected in the GIC layer. Hardness in the Safo+Fuji group was significantly higher compared with the Safo group at depths in the range of 10–50 µm. ConclusionIn the presence of GICs, SDF exhibited high remineralization capacity when diffusing throughout carious lesions over time. Combined treatment with SDF and GIC could strengthen root dentin even in the presence of caries. Clinical significanceWe found that combination treatment with SDF and GIC could increase mineral density in caries and improve the hardness of the tooth structure compared with fluoride-based agents alone. These findings might pave the way for future clinical trials to determine the therapeutic potential of nanotechnology-based restorative materials.