Objectives: The objective of the present study was to evaluate the ability of a novel self-assembling peptide containing desensitizing gel with fluoride and calcium phosphate for dentine tubule occlusion compared to selected leading desensitizing toothpastes. Methods: Mid-coronal dentine discs with a thickness of 1 mm were sectioned from caries-free human molars. The discs were etched with 6% citric acid for 2 minutes, halved and subjected to a 2-minute brushing with the gel and three selected leading desensitizing toothpastes (Sensodyne® Repair and Protect [SRP], Sensodyne® Rapid Relief [SRR] and Colgate® Sensitive ProReliefTM [CSP]). The ability of the desensitizing gel and toothpastes to occlude the dentine tubules was studied and compared before and after brushing using Scanning Electron Microscopy (SEM) on both etched and fractured dentine surface. The SEM observations were supplemented by hydraulic conductance measurements using a modified Pashley model before and after tooth brushing (n=5). Results: Dentine tubules occlusion with a reduction in the number and the size of open dentine tubules was evident for all the treated dentine discs. The particles that occluded the open dentine tubules had different morphologies and distribution. The self-assembling peptide containing gel demonstrated the most remarkable reduction in the number of open tubules. Reductions in the dentine hydraulic conductance measurements were observed for all tested materials (mean [SD, %]: Gel 55.1 [12.5], SRP 64.9 [18.5], SRR 39.1 [17.1] and CSP 27.6 [6.8]). No statistically differences were observed between the Gel and SRP, SRR and CSP toothpastes (paired t-Test; ≤0.05), the reduction for the Gel was however significantly higher than the SRR and CSP toothpastes. Conclusion: The results suggest that a novel self-assembling peptide containing gel was effective in blocking the dentine tubules and may therefore be a suitable desensitizing product for the treatment of Dentine Hypersensitivity.