Magnesium (Mg) and strontium (Sr) have been widely used in the field of implanted devices because of their excellent bioactivity. However, the local high ion concentration caused by the implant affects the growth of hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, HA), which is the main inorganic component of bone and teeth. Many studies have investigated the effect of Mg²⁺ and Sr²⁺ on the growth of HA, but no systematic research has been conducted to compare these two ions in terms of the growth of HA. In this study, the substitution of a series of Sr- and Mg-substituted HA was conducted through a conventional hydrothermal method. Comprehensive characterization techniques, including X-ray diffraction, inductive coupled plasma, field emission scanning electron microscopy, transmission electron microscopy, selected-area electron diffraction, thermo gravimetric-differential scanning calorimetry, and Fourier transform infrared spectroscopy, were used to examine the effects of Sr²⁺ and Mg²⁺ on the phase, morphology, crystallinity, chemical composition, thermal stability, and lattice parameters of HA. The results indicated that Mg ions partially substituted for calcium (Ca) ions in the apatite structure, thus decreasing the lattice parameters, partially adsorbing on the apatite surface that formed the amorphous phase, and inhibiting the crystal growth. By contrast, Sr ions fully substituted for Ca ions and increased the lattice parameters. Both Mg and Sr ions affected the morphology of HA. Crystallinity decreased with the addition of Mg ions (transition from the crystal to amorphous phase was between 30% and 40% Mg), but it was not affected by Sr ions. Thermostability decreased with the addition of Mg (a total weight loss from 8.06 wt% for 10% Mg to 25.81 wt% for 50% Mg), but it had no significant changes in the Sr-substituted samples.