ObjectivesThe objective of this study was to investigate enamel remineralization using salivary statherin protein-inspired poly(amidoamine) dendrimer (SN15-PAMAM) and adhesive containing nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/demineralizing solution for the first time. MethodsThe enamel shear bond strengths of NACP adhesives were measured compared to commercial adhesive (Scotchbond Multi-Purpose, 3 M). Adhesive disks containing NACP were tested for calcium (Ca) and phosphorus (P) ions release. Four groups were tested: (1) enamel control, (2) enamel with NACP, (3) enamel with SN15-PAMAM, and (4) enamel with SN15-PAMAM + NACP. The specimens were treated with cyclic artificial saliva/demineralizing solution for 28 days. The remineralized enamel specimens were examined by surface and cross-sectional hardness test. ResultsNACP adhesive yielded a similar shear bond strength to commercial control (Scotchbond Multi-Purpose, 3 M). NACP adhesive released high levels of Ca and P ions. At 28 days, the enamel hardness of SN15-PAMAM + NACP group was 2.89 ± 0.13 GPa, significantly higher than that of control group (1.46 ± 0.10 GPa) (p < 0.05). SN15-PAMAM + NACP increased the enamel cross-sectional hardness at 28 days; at 25 μm, enamel cross-sectional hardness was 90 % higher than that of control group (p < 0.05). SignificanceThe novel SN15-PAMAM + NACP adhesive method could achieve 90 % higher enamel remineralization of the artificial caries than the control under acid challenge for the first time. This method is promising for use after tooth cavity preparation, or as a coating on enamel with white spot lesions (WSLs) for prevention, to reduce secondary caries, prevent caries procession and protect tooth structures.