Purpose: The present study was performed to evaluate the combined effect of Hydrogel desensitizer with other two desensitizing materials namely an oxalate derivative (Bis-Block) and Casein phosphopeptide-calcium phosphate complex (Tooth Mousse) on dentin permeability. Materials and Methods: Sixty radicular dentin discs of 1 mm thickness were prepared from large non carious third molar teeth. The discs were divided into 3 main groups (20 specimens each) according to the application of desensitizing agents (D).Each group was further subdivided into 2 subgroups according to the application of Hydrogel (H) .Before application of the materials, etching of the dentin discs and measuring the dentinal permeability as a baseline had been done using fluid transport apparatus. Each desensitizing agent was applied according to its manufacturer recommendations. After application of desensitizing materials separately and in combination to Hydrogel, dentinal permeability was measured again to quantitatively investigate the dentinal sealing ability of the used desensitizing agents. Dentinal tubules obliteration was also examined under scanning electron microscopy SEM. Dentin permeability results were statistically analyzed using IBM®SPSS® Statistics Version 20 for Windows. Results: dentin permeability revealed that there was a statistically significant difference between the five groups. The oxalate derivative (Bis Block) showed the statistically significant lowest mean permeability percentage change, while the combined effect of Hydrogel application after oxalate desensitizer had a statistically significant reduction in permeability percentage of dentin. There was no statistically significant difference between oxalate with Hydrogel, CPP-ACP, CPP-ACP with Hydrogel and Hydrogel groups; all showed the statistically significantly highest mean permeability percentage change. Conclusions: 1- Casein phosphopeptide-amorphous calcium phosphate has a potent occluding effect on dentinal tubules with subsequent decrease of dentin permeability. 2-Oxalates as a desensitizing agent has limited ability to completely obliterate the dentinal tubules. 3-Hydrogel can augment the obliterating capacity of the oxalate desensitizing agent.