OBJECTIVE This study determined the potency of resin infiltrations and resin sealant in impeding microleakage on artificial white-spot lesions (AWL) by methylene blue penetration. METHODS Eighty AWL specimens were randomly separated into two groups for water storage for 24 hours (groups 1-4) and 20,000 cycles of thermocycling (TC) (groups 5-8). Each group was then separated into four subgroups (n = 10) based on the AWL surface treatments: (1) no Tx, (2) treated with resin infiltration (ICON, DMG, Hamburg, Germany), (3) treated with resin infiltration (Surface pre-reacted glass-ionomer (S-PRG) barrier coat, SHOFU, Kyoto, Japan), (4) treated with resin sealant (Clinpro sealant, 3M ESPE, Minnesota, United States). Nail varnish was covered to all samples, with the exception of a 4 × 4 mm2 patch on the buccal measurement region, which was subsequently submerged in a 2% methylene blue solution and cut into buccolingual sections. Stereomicroscope measurements were used to calculate methylene blue penetration scores. METHODS The Kruskal-Wallis test and the Bonferroni post-hoc correction were performed to evaluate the data. RESULTS Application of resin infiltrants and resin sealant reduced microleakage in AWL by methylene penetration both before and after thermal cycling. In addition, group 6 (ICON + TC) and group 7 (S-PRG + TC) had a significantly different value from group 8 (sealant + TC). CONCLUSIONS Both the resin infiltration approach and the resin sealant seem to help seal AWL and might perhaps offer long-term defense against microleakage in AWL caused by methylene blue penetration. The greatest sealing and defense for microleakage in AWL were demonstrated by the resin infiltrations.