Objectives: To estimate the dentinal tubules occlusion potential of biomimetic materials as nano-hydroxyapatite and self-assembling peptides and to compare their results with a traditionally used sodium fluoride material.Materials and methods: Standardized forty dentin disks were obtained from extracted molars. They were treated with citric acid 6% for 2 min to simulate the hypersensitive dentin. Disks were classified into four equal groups (n=10); Control group without treatment; Sodium fluoride (Bifluorid 10, VOCO, Germany); self-assembling peptide (CurodontTM Protect, Credentis, Switzerland) or nanohydroxyapatite nHAp containing material (Remin Pro, VOCO, Germany). Fluoride varnish was applied twice during the test period (7 days) and the biomimetic desensitizing agents were left for 5 minutes/ once daily. Specimens were stored in artificial saliva during the seven days. Specimens were analyzed using scanning electron microscope (500X). Quantitative analysis of the surface area (µm2) of the patent dentinal tubules in the scanned images was done by using digimizer image analysis software (version 3.7.0.0). Statistical analysis was done using One way-ANOVA followed by Tuckey’s post hoc test for comparison (P≤ 0.05).Results: In the control group, the dentinal tubules were widely opened after being demineralized with the highest dentinal tubules mean surface area recorded (592.5±68.0 µm2). Sodium fluoride group revealed partially obliterated dentinal tubules with intratubular deposits leaving a mean surface area of 260.0± 53.3 µm2. Opened areas in the fluoride group are statistically equal to those in the self-assembling peptide group (203.5±99.3). In the nanohydroxyapatite group, almost complete sealing of the dentinal tubules was evident with the least mean surface area of the opened parts(35.0±5.3). The difference between the study groups was statistically significant. Conclusions: The desensitizing agents studied showed different abilities to change the dentin surface micromorphology, with partial or total occlusion of dentinal tubules. Nanohydroxyapatite containing agent is a promising biomimetic material for management of dentin hypersensitivity.