Objectives: To compare the ability of resin-modified glass ionomer (RMGI) and bioactive cements to prevent root dentin demineralization. Materials and Methods: Fifty molars were prepared at the cementum-enamel junction (n = 10) and restored with three bioactive cements (Activa Bioactive Cement, ACT; Ceramir Crown and Bridge, CER; and Theracem, THE), a self-adhesive resin cement (Rely X Unicem 2, UNI), and a RMGI cement (Rely X Luting Plus, LUT). Specimens were cycled for 30 days between a demineralization solution (pH = 4) composed of 0.1 M lactic acid and 3 mM Ca3(PO4)2 for 4 hours and a remineralization solution (pH = 7.0) composed of 1.5 mM Ca, 0.9 mM P, and 20 mM Tris(hydroxymethyl)-aminomethane for 20 hours. Specimens were sectioned to 100 μm and evaluated with polarized light microscopy. A line was drawn parallel with the zone of demineralization for each tooth. The areas of “inhibition” (external to the line) were measured as positive values and “wall lesions” (pulpal to the line) were measured as negative areas. Results: Significant differences were found between materials for “inhibition/wall lesion” areas in root dentin (P <.001) and ranked as (μm2, mean ± SD): LUT (7700 ± 2500) > CER (3800 ± 1900), THE (2100 ± 2600), and ACT (1400 ± 700) > UNI (−2000 ± 1700). Conclusions: Bioactive cements showed net areas of demineralization inhibition albeit at a lower level than a reference RMGI cement. Clinical Significance: RMGI or bioactive cements may be indicated for patients at risk of secondary caries around crown margins.