The effect of a surface pre-reacted glass ionomer (S-PRG)-containing sealant on the demineralization inhibition and remineralization of intact enamel adjacent to the sealant material was investigated. BeautiSealant (BTS, S-PRG sealant, Shofu), Teeth Mate F-12.0 (TMF, fluoride-releasing sealant, Kuraray Noritake Dental), and an experimental silica-filler sealant were investigated. After pH cycling for 10 days, the enamel surface adjacent to the sealant material was observed using confocal laser microscopy and scanning electron microscopy. The polymerized sealant disks were immersed in a demineralized solution (pH: 4.3) to measure pH change. The enamel specimens with polymerized sealant disks were additionally immersed in demineralized solution, followed by energy-dispersive X-ray spectroscopy. The demineralized area of BTS was significantly smaller than that of TMF and SS (p < 0.05). The surfaces adjacent to the sealant of TMF and SS were demineralized, while the surface of BTS was comparatively intact. An increase in pH values were observed in the BTS and TMF groups. Enamel surfaces presented an inhibition of demineralization for BTS and TMF, but not for SS. Fluoride uptake from the polymerized sealant was greater for BTS than for TMF. The S-PRG-containing sealant showed a buffering ability, demineralization inhibition, promotion of remineralization, and it can be advised for clinical applications.