This study used sol-gel and hydrothermal methods to prepare binary bioactive glasses (BG) of SiO2-CaO with 63% and 37% molar fractions, respectively. Different techniques characterized heat-treated powders: Thermogravimetric analysis (TGA), Fourier-transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, inductively coupled plasma-atomic emission analysis (ICP-AES), solid-state nuclear magnetic resonance (NMR), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), and Brunauer-Emmett-Teller analysis (BET). According to both synthetic routes, the HT technique presented better new apatite layers deposition on BG particles during in vitro bioactivity assessment in simulated body fluid (SBF). The bioactivity is confirmed by XRD analysis, NMR spectroscopy, and BET analysis showing that HT-derived bioactive glass (BG-HT) presents higher bioactivity than sol-gel-derived BG (BG-SG), and the nanometric particle size of HT-BG (90-100 nm) with a high specific surface area is responsible for this enhancement. Furthermore, NMR spectroscopy indicates the higher network connectivity of HT-derived bioactive glass due to different environments in this structure. Moreover, SEM-EDS micrographs of BG-HT glasses show spherical nanoparticles, while BG-SG results present a mixture of spherical and rod-like microparticles. The HT-BG could be a promising material for biomedical applications, especially in drug delivery and ion release.