Objective: To compare the in vitro potential of dentin tubule occlusion of two novel experimental dentifrices consisting of fluoride containing bioactive glass (BG) with zinc oxide nanoparticles. Materials and Methods: Forty-eight dentin discs (n = 48) were divided into 6 groups (n = 8), based on their brushing dentifrices: Group 1 = artificial saliva (AS; control); Group 2 = fluoride dentifrice (Colgate Palmolive^©, UK); Group 3 = experimental nonactive agent dentifrice; Group 4 = experimental dentifrice with 1.5% BG; Group 5 = experimental dentifrice with 4% BG; and Group 6 = BioMinF^© dentifrice. Postbrushing, the discs were subjected to acidic challenge with 6% wt citric acid (pH = 4.0) for 1 min. Scanning electron microscope (SEM) and energy-dispersive X-ray (EDX) spectroscopy were performed pre- and post-citric acid challenges, and percentages of tubule occlusion assessed. Results: SEM micrographs of group 1 (AS) show no tubule occlusion (0%), whereas those of groups 2 and 3 show partial tubule occlusion (25 to <50% of tubules occluded). The SEM micrographs of dentifrices containing fluoride-BG (groups 4, 5, and 6) show that most of the tubules (>50 and <100%) were occluded. For all the groups (excluding group 1), pre- and post-citric acid challenge values are statistically significant (p < 0.05). EDX analysis reveals the presence of zinc in experimental dentifrices only. Conclusion: The results of novel experimental dentifrices are comparable to those of the BioMinF^©, in terms of tubule occlusion. Dentifrices containing BG could serve as an alternative in dentin sensitivity management.