The aim of this work was to study the influence of the different synthesis processes on microstructural and morphological characteristics and distribution of hydroxyapatite-bioactive glass (HAp-BG) composite nanopowders obtained by sol–gel method. HAp-BG composite nanopowders with 20 wt% bioactive glass were prepared using a sol–gel method via four routes: (I) mixing the prepared HAp solution with BG solution before aging time; (II) mixing the prepared BG solution with the prepared HAp gel after gelation; (III) mixing the calcined BG nanopowders with the prepared HAp solution; and (IV) mixing the two prepared calcined nanopowders by mechanochemical activation. The prepared nanopowders were evaluated and studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometer (EDS), Fourier transform infrared (FTIR), transmission electron diffraction (TEM) and Brunauer–Emmet–Teller (BET) method to investigate the phase structure, microstructure and morphology, functional groups, and the size and distribution of nanopowders. Results indicated that morphology, crystallinity, crystallite size and specific surface area (SSA) of the powders are highly correspondent to the process and type of synthesis method. These findings suggest that the modified sol–gel derived HAp-BG composite nanopowders are expected to efficiently provide a possibility to produce a good candidate to use for fabrication of a bulk nanostructured HAp-BG composite for bone tissue engineering.