Whitlockite (WH, Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂) is an important inorganic phase in human bones and has positive significance for participating in the bone reconstruction process. In this paper, we report different doping strategies to prepare WH and WH-Ln (Eu/Tb) nanocrystals, and have successfully synthesized WH-Ln (Eu/Tb) nanoparticles (NPs) with bright red or green fluorescence based on ions exchange doping by two-step hydrothermal reaction. WH-5%Ln (Eu/Tb) NPs with the best fluorescence properties were successfully applied to live cell imaging, and WH-5%Eu NPs were implanted into the bone defect site in rabbit femoral condyles to visually observe its degradation process. The related results would help us understand WH nanocrystals and further expand their potential applications in tissue engineering and related fields.