Context:Dental hypersensitivity and loss of dental tissues are commonly observed in patients, and most of the problems are caused due to total or partial exposure of dentinal tubules.Aims:The purpose of this study is to evaluate the performance of 45S5 bioactive glass and niobophosphate (NbG) associated with neodymium: yttrium-aluminum-garnet (Nd:YAG) laser for the reduction of dentin permeability.Materials and Methods:Fifty bovine dentin discs were made and distributed randomly into five groups (n = 10). The Nd:YAG laser was applied with the bioactive glasses using the energy parameters (60 and 80 mJ), forming the groups; NbG_60: NbG + Nd:YAG (60 mJ); NbG_80: NbG + Nd:YAG (80 mJ), 45S5_60: 45S5 + Nd:YAG (60 mJ); 45S5_80: 45S5 + Nd:YAG (80 mJ) and C: control (untreated dentin). The permeability was measured with a split chamber device. The samples were subjected to the erosive challenge and a new permeability measurement was done. Furthermore, the dentin was analyzed by scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS).Statistical Analysis Used:The data were analyzed using Kruskal–Wallis and Dunn's tests (α = 0.05).Results:Greater reduction in dentinal permeability was observed for 45S5 bioactive glasses (45S5_60 and 45S5_80) followed by NbG_80 and NbG_60 (P < 0.05). The SEM/EDS analysis showed the formation of a barrier after the dentin treatment.Conclusions:Bioactive glasses with Nd:YAG laser on the dentin surface may be a promising alternative for the reduction of dentin permeability.