The purpose of this in vitro study was to evaluate and compare the efficacy of erbium-doped yttrium aluminum garnet (Er:YAG) laser, neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, PrevDent nano-hydroxyapatite toothpaste plus Repairing Serum Kit (PNH), and NUPRO Sensodyne Prophylaxis Paste with NovaMin (NPP) on dentin permeability reduction. Forty dentin discs obtained from bovine incisors were divided into four study groups: Er:YAG laser-treated (2940nm; 0.2W, 80mJ/pulse, 3Hz); Nd:YAG laser-treated (1064nm; 1W, 10Hz); PNH-treated; and NPP-treated groups. The quantitative changes in permeability of each dentin disc were measured using a computerized fluid filtration method (CFFM) before and after desensitizer treatments. The data were analyzed using the Wilcoxon, paired-samples t, Kruskal-Wallis, and Mann-Whitney U tests. The dentin surfaces and tubules were also morphologically detected by scanning electron microscopy (SEM). In all groups, dentin permeability was significantly reduced after the desensitizer and laser treatments (p<0.05). Among the groups, we detected a significant difference in only when comparing the Er:YAG laser- and NPP-treated groups (p=0.034). SEM analysis revealed physical changes in the dentin surface in all groups. This in vitro study shows that all tested desensitizers and laser treatments reduced dentin permeability. Also, surface changes, such as complete or partial occlusion or shrinkage of dentin tubules, were observed in all groups. Although the laser groups performed best, the PNH protocol can be considered as an alternative therapeutic product. In addition, clinical and laboratory studies should be performed for this product, and their efficacy should be assessed by combined therapy with lasers.