This study aimed to evaluate potential impacts of calcium oxide nanoparticles (CaO-NPs) at different dosages on predentin thickness, number of blood vessels, periodontal ligament thickness, and blood glucose level of Wistar rats. Twelve rats were randomly gathered into four groups, untreated (control) and CaO-NP-treated groups at three concentrations (25, 50, and 100 mg/kg of the body weight) over a period of 60 days. Histological investigation was performed on twenty-four lower incisor teeth extracted from all the tested groups under a light microscope, and an automatic Fujifilm was used to measure the blood glucose level. The results showed that regular nanoparticle treatment significantly increased predentin and periodontal ligament thicknesses, a gradual decrease in vascularization in the pulp tissue, and an increase in the blood glucose level as the dosages of nanoparticles administered to the rats increased. Administration of the CaO-NPs at low dosage (25 mg/kg) could be beneficial for the growth and integrity of teeth and dentinal tissues in rats.