Calcium and vitamin D are essential for combating osteoporosis.However, enhancing the anti-osteoporosis effects of the supplements remains a challenge.This study introduced an optimized multiple emulsion micro-reaction method for preparing vitamin D3/calcium phosphate microparticles.The microstructure and characteristics of vitamin D3/hydroxyapatite microparticles (VD3@HAP) and vitamin D3/calcium hydrophosphate microparticles (VD3@CHP) were analyzed using Fourier transform IR (FTIR) spectroscopy, X-ray diffraction (XRD), SEM (SEM), and stress testing.The calcium absorption and anti-osteoporosis effects of VD3@HAP and VD3@CHP were evaluated in situ and in vivo, resp.FTIR and XRD analyses confirmed that the microparticles retained the spectral characteristics of calcium phosphates, while VD3@HAP exhibited randomly distributed pores on its surface, enhancing both the loading capacity and photostability of vitamin D3 compared to VD3@CHP.Addnl., the vitamin D3/calcium phosphate microparticles prepared by this method significantly increased bone mineral d. and decreased serum alk. phosphatase levels.Notably, VD3@HAP demonstrated superior calcium absorption, reduced marrow cavity area, and improved osteoporosis symptoms in the rat model compared to VD3@CHP, as evidenced by absorption assay, X-ray anal., and HE staining.Thus, the multiple emulsion micro-reaction method effectively prepared vitamin D3/calcium phosphate microparticles that enhanced the anti-osteoporosis effects of supplementation, particularly VD3@HAP.We anticipate that VD3@HAP could serve as a safe and effective calcium supplement with significant potential for preventing and treating osteoporosis.