A thermodynamic evaluation was performed to predict phase separation in multi-component oxide glasses. Composition ranges for metastable liquid–liquid immiscibility and spinodal decomposition in a SiO₂–CaO–MgO–Na₂O quaternary system were calculated on the assumption that glasses in the oxide system can be regarded as super-cooled liquid phases. Some experimental studies on two-phase separation of glasses were carried out to confirm the thermodynamic evaluation of the phase separation. Microstructures in heat-treated glass samples were observed by transmission electron microscopy, to investigate the development of interconnected microstructures in the glass with increased heating temperatures and holding times, and spinodal decomposition of glass was indicated.