Nanotechnologyis the art and science of dealing with nanoscale particles. This has transformed contemporary dental practices through myriad contributions to biomaterial science. Titanium dioxide nanoparticles procured from Bacillus subtilis, an eco-friendly and biogenic source, can significantly magnify the physiochemical attributes of dental materials. However, postoperative sensitivity is a major drawback of composite restorations. The incorporation of these nanoparticles into dental adhesives can greatly benefit clinical dentistry by resolving this issue. This trial aimed to evaluate the effectiveness of a novel titanium dioxide nanofortified adhesive on the postoperative sensitivity of composite restorations.MethodsThis triple-blind, parallel-group randomized controlled trial was conducted at the Department of Operative Dentistry and Endodontics, School of Dentistry, Islamabad, from May 15, 2023, to November 25, 2023. Participants (n = 60) with Class I and II primary carious lesions with a minimum cavity depth of 3–5 mm were randomly assigned to two groups (n = 30). After obtaining informed consent, the restorative procedure was accomplished using a minimally invasive approach and etch-and-rinse adhesive strategy. In group A, a nanofortified adhesive was used for composite restoration, whereas in group B, an adhesive without nanoparticles was used. Postoperative sensitivity was evaluated using the Visual Analog Scale (VAS) score at follow-up periods: of one day, one week, two weeks and one month. A Chi-square test was used to compare postoperative sensitivity between the two groups. The level of significance was set at p < 0.05.ResultsA noteworthy association was observed between sensitivity and the group variable at all four evaluation periods: after one day (p = 0.002), 1 week (p = 0.002), 2 weeks (p = 0.007) and one month. In conclusion, participants who underwent restorative intervention using titanium dioxide nanoreinforced adhesives reported a notable reduction in sensitivity at all time intervals. Hence, the occurrence and severity of postoperative sensitivity are significantly reduced using Bacillus subtilis-procured nanofortified adhesives as compared to conventional adhesives without nanoparticles.Trial registrationThis trial was retrospectively registered at ClinicalTrials.gov (ID: NCT06242184) on 03/02/2024. All procedures involving human participants were performed in conformance with this protocol.