Biological apatites contain many substitutions (i.e. F - , CO3 2- , Na + , Mg +2 , Zn +2 ). Properties of hydroxyapatite (HA) or fluorapatite (FA), such as bioactivity, biocompatibility, solubility, and adsorption properties can be tailored over a wide range by modifying the composition via ionic substitutions. The aim of this work was preparation and characterization of Mg-doped FA (Mg-FA) nanopowders. Mg-FA nanopowders with different Mg content were prepared by sol–gel method. The designated degree of substitution of Ca2+ by Mg2+ in the mixture was indicated by the x value in the general formula of (Ca10?xMgx (PO4)6F2), where x= 0, 0.25, 0.5 , 0.75, and 1. Mg-FA nanopowders with different Mg content were also prepared by mechanical alloying (MA) method. The designated degree of substitution of Ca2+ by Mg2+ in the mixture was indicated by the x value in the general formula of (Ca10?xMgx (PO4)6F2), where x= 0, 0.5, 1, 1.5, and 2. X-ray diffraction (XRD), scanning electron microscopic (SEM), atomic absorption spectrophotometer (AAS), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) techniques were utilized to characterize the obtained powders. In vitro bioactivity evaluation of powders were investigated by soaking the powders in simulated body fluid (SBF) for predicted various time periods in order to analyze the nucleation and growth of bone-like apatite (carbonate-containing hydroxyapatite) on the surface of the powders. FTIR, SEM and AAS techniques were utilized to identify and characterize the formed bone-like apatite on the obtained powders. Results indicated that Mg ions entered into the fluorapatite lattice and occupied Ca 2+ sites and obtained powders had crystallite size about 30–100 nm. With increasing the Mg-substitution, the solubility of powders and the adsorption of Ca 2+ ions onto the powders surfaces increased, simultaneously. It was concluded that Mg-substitution improves the bioactivity of FA, and the bioactivity is proportional to Mg concentration of powders