Patients with dry mouth often have an acidic oral environment lacking saliva to provide calcium (Ca) and phosphate (P) ions. There has been no report on tooth remineralization in acidic pH4 and CaP ion-lacking solutions. The objective of this study was to develop a novel method of combining poly(amido amine) (PAMAM) with adhesive containing nanoparticles of amorphous calcium phosphate (NACP) for dentin remineralization in pH4 and CaP-lacking solution for the first time. Demineralized dentin was tested in four groups: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP adhesive, (4) dentin with PAMAM + NACP adhesive. Dentin samples were examined by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and hardness testing. Increasing the NACP filler level in adhesive from 0 to 40 wt% did not negatively affect the dentin bond strength (p > 0.1). NACP adhesive released CaP ions and neutralized the acid. PAMAM alone failed to achieve dentin remineralization in lactic acid. NACP alone induced slight dentin remineralization in lactic acid (p > 0.1). In contrast, the novel PAMAM + NACP group in the pH4 and CaP-lacking solution completely remineralized the predemineralized dentin, increasing its hardness which approached that of healthy dentin (p > 0.1). In conclusion, dentin remineralization via PAMAM + NACP adhesive in pH4 and CaP-lacking acid was achieved for the first time, when conventional remineralization methods such as PAMAM or NACP did not work. The novel PAMAM + NACP method is promising to increase the longevity of the composite-tooth bond, inhibit caries, remineralize lesions and protect tooth structures, even for patients with dry mouth and an acidic oral environment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2414-2424, 2018.