Enameldemineralization adjacent topitandfissuresealants leads to the formation of marginal caries, which can necessitate the replacement of existing sealants. Dental materials withbioactiveglass, which releases ions that inhibit dental caries, have been studied. The purpose of this study was to evaluate theenamelsurfaceadjacent to sealantscontaining45S5bioactiveglass(BAG) under simulated microleakage between the material and the tooth in a cariogenic environment. Sealantscontaining45S5BAG filler were prepared as follows: 0% 45S5BAG + 50.0%glass(BAG0 group), 12.5% 45S5BAG + 37.5%glass(BAG12.5 group), 25.0% 45S5BAG + 25.0%glass(BAG25.0 group), 37.5% 45S5BAG + 12.5%glass(BAG37.5 group), and 50.0% 45S5BAG + 0%glass(BAG50.0 group). A curedsealantdisk was placed over a flat bovineenameldisk, separated by a 60-µm gap, and immersed in lactic acid solution (pH 4.0) at 37 °C for 15, 30, and 45 d. After the storage period, eachenameldisk was separated from the curedsealantdisk, and theenamelsurfacewas examined with optical 3-dimensionalsurfaceprofilometer, microhardness tester, and scanning electron microscopy. The results showed a significant increase in roughness and a decrease in microhardness of theenamelsurfaceas the proportion of 45S5BAG decreased (P< 0.05). In the scanning electron microscopy images,enamelsurfaces with BAG50.0 showed a smoothsurface, similar to those in the control group with distilled water, even after prolonged acid storage. Additionally, an etched pattern was observed on thesurfaceof the demineralizedenamelwith a decreasing proportion of 45S5BAG. Increasing the 45S5BAG filler contents of the sealants had a significant impact in preventing the demineralization of theenamelsurfacewithin microgaps between the material and the tooth when exposed to a cariogenic environment. Therefore, despite some marginal leakage, these novel sealants may be effective preventive dental materials for inhibiting secondary caries at the margins.