Whitlockite (WH, Ca18Mg2(HPO4)2(PO4)12) is the second most abundant biomineral in human bone and has attracted attention as a novel bone regenerative material. It has been proven to enhance growth and promote osteogenesis of stem cells. However, investigating the mechanism of crystal formation in pure phase WH nanocrystals remains a challenge. In this study, a novel synthesis method of WH nanocrystals is introduced using a tri-solvent system of solid-liquidsolution (SLS). Computational finite element method (FEM) simulations were carried out to reveal the solvent effect in the reaction. The cell proliferation and alkaline phosphatase (ALP) activity assay of human bone marrow derived mesenchymal stem cells (hBMSCs) demonstrated that WH can enhance the proliferation and promote the osteogenic activity of stem cells in comparison with HAP. The as-synthesized WH using our novel reproducible and robust methods has great potential for future use in osteogenic tissue engineering.