This study evaluated the effect of different types of filler in a resin-based pit and fissure sealant on fluoride release, recharge, and lactic acid neutralization. Resin-based sealant was incorporated with 5% w/w of the following fillers: calcium aluminate cement (CAC), synthesized mesoporous silica (SI), a CAC and SI mixture (CAC+SI), glass-ionomer powder (GIC), and acetic acid-treated GIC (GICA). Sealant without filler served as control. The samples were immersed in deionized water or a lactic acid solution and the concentration of fluoride in the water, before and after fluoride recharge, and the lactic acid pH change, respectively, were determined. The CAC+SI group demonstrated the highest fluoride release after being recharged with fluoride gel. The CAC+SI group also demonstrated increased lactic acid pH. These findings suggest that a resin-based sealant containing synthesized mesoporous silica and calcium aluminate cement may enhance remineralization due to fluoride release and higher pH.