When dentin is directly exposed to the oral cavity for various reasons, such as a lack of enamel on the tooth surface, external stimuli to the dentin often cause transient discomfort known as dentin hypersensitivity. In order to block the incoming stimulus signal, an ideal treatment is to induce the production of minerals to block the dentinal tubules. In this work, a dentin-desensitizing plugging material was prepared by modifying mesoporous bioactive glass with gelatin, the mineralization and desensitization effects of which were compared with Gluma in in vitro experiments. These experiments confirmed that gelatin-modified bioactive glass (MBG@PDA@Gel) is more effective than traditional desensitizing agents at blocking dentin tubules. Following the successful synthesis of MBG@PDA@Gel, as confirmed by scanning electron microscopy, transmission electron microscopy, and other tests, the treatment of demineralized dentin with MBG@PDA@Gel demonstrated that the dentinal tubules were tightly blocked under scanning electron microscopy. MBG@PDA@Gel induces minerals in deeper layers of dentinal tubules, promoting remineralization and forming a unified structure with the tubule blockage. Animal studies showed that MBG@PDA@Gel can remineralize demineralized dentin, and it is stable in the oral cavity and does not fall out. MBG@PDA@Gel not only enhances the biocompatibility of the nanoparticle but also results in an overall uniform and rapid remineralization of the demineralized dentin.