The fabrication of enamel-mimicking material for clinical enamel remineralization remains a challenge. In this work, we proposed a facile and economical biomimetic strategy for achieving in vitro hydroxyapatite (HAP) remineralization on eroded human enamel using nacre water-soluble matrix (WSM) as template. X-ray diffraction (XRD) analysis and Fourier transformed infrared (FTIR) spectroscopy demonstrated that WSM facilitated the formation of HAP with a similar composition and structure to the natural enamel under mild conditions. Microscopic investigations revealed that the WSM-induced HAP nanorods were well bundled in parallel and densely arranged into highly-ordered units as compared to loose and disordered HAP crystals formed in the absence of WSM. The ideal features, smoothness and hardness of the WSM-induced HAP were further confirmed by the atomic force microscope (AFM) and digital Vicker's Hardness tester. We also discussed the role of WSM in inducing the highly-ordered HAP. The finding in this work provides new threads for the development of novel dental materials for clinical caries management.