ObjectiveThis study investigates the effects of nano-hydroxyapatite (NHA) gel and Clinpro (CP) on remineralization potential of enamel and cementum at the cavosurface area of computer-aided design and computer-aided manufacturing ceramic restoration.Materials and methodsThirty extracted human mandibular third molars were sectioned at 1 mm above and below the cemento–enamel junction to remove the cemento–enamel junction portions and replaced them with zirconia ceramic disks by bonding them to the crown and root portions with resin cement. The enamel and cementum with an area of 4×4 mm2 surrounding the ceramic disk was demineralized with carbopol. The demineralized surfaces were treated with either NHA or CP, while 1 group was left with no treatment. Vickers microhardness of enamel and cementum were determined before demineralization, after demineralization, and after remineralization. Analysis of variance and Tukey multiple comparisons were used to determine statistically significant differences at 95% level of confidence. Scanning electron microscopy and X-ray diffraction were used to evaluate for surface alterations.ResultsThe mean ± SD of Vickers microhardness for before demineralization, after demineralization, and after remineralization for enamel and cementum were 377.37±22.99, 161.95±10.54, 161.70±5.92 and 60.37±3.81, 17.65±0.91, 17.04±1.00 for the no treatment group; 378.20±18.76, 160.72±8.38, 200.08±8.29 and 62.58±3.37, 18.38±1.33, 27.99±2.68 for the NHA groups; and 380.53±25.14, 161.94±5.66, 193.16±7.54 and 62.78±4.75, 19.07±1.30, 24.46±2.02 for the CP groups. Analysis of variance indicated significant increase in microhardness of demineralized enamel and cementum upon the application of either NHA or CP (p<0.05). Post hoc multiple comparisons indicated significantly higher remineralization capability of NHA for both enamel and cementum than CP (p<0.05), as evidenced by scanning electron microscopy, indicating NHA particle deposition in the area of remineralization, and crystallinity accumulation, as indicated by X-ray diffraction.ConclusionNHA gel and CP were capable of remineralization of the enamel and cementum. NHA was more capable in the remineralization process than CP. NHA was extremely capable in the remineralization process for enamel and cementum surrounding the margin of the computer-aided design and computer-aided manufacturing ceramic.