Demineralized white lesions are a common problem when using orthodontic resin cement, which can be prevented with the addition of antibacterial substances. However, the addition of antibacterial substances such as zinc oxide alone may result in the deterioration of the resin cement’s functions. Halloysite nanotubes (HNTs) are known to be biocompatible without adversely affecting the mechanical properties of the material while having the ability to load different substances. The purpose of this study was to prepare orthodontic resin cement containing HNT fillers loaded with ZnO (ZnO/HNTs) and to investigate its mechanical, physical, chemical, and antibacterial properties. A group without filler was used as a control. Three groups containing 5 wt.% of HNTs, ZnO, and ZnO/HNTs were prepared. TEM and EDS measurements were carried out to confirm the morphological structure of the HNTs and the successful loading of ZnO onto the HNTs. The mechanical, physical, chemical, and antibacterial properties of the prepared orthodontic resin cement were considered. The ZnO group had high flexural strength and water absorption but a low depth of cure (p< 0.05). The ZnO/HNTs group showed the highest shear bond strength and film thickness (p< 0.05). In the antibacterial test, the ZnO/HNTs group resulted in a significant decrease in the biofilm’s metabolic activity compared to the other groups (p< 0.05). ZnO/HNTs did not affect cell viability. In addition, ZnO was cytotoxic at a concentration of 100% in the extract. The nanocomposite developed in this study exhibited antimicrobial activity againstS. mutanswhile maintaining the mechanical, physical, and chemical properties of orthodontic resin cement. Therefore, it has the potential to be used as an orthodontic resin cement that can prevent DWLs.