This study is to investigate the effect of synthesis approaches on morphology, porosity, and biocompatibility of bioactive glass (BG). BG prepared through sol–gel approach was subsequently subjected to microwave and probe sonication techniques to investigate the structural and morphological effect. Hexagonal rod‐shaped morphology was obtained in sol–gel‐derived bioactive glass, whereas mesoporous particles and spherical‐shaped morphology were observed in probe‐sonicated and microwave‐assisted sol–gel approaches, respectively. The probe‐sonicated BG has mesopores with pore diameter of 14.7 nm, whereas surface porosity of 1.5 nm, and 3.5 nm for pure sol–gel and microwave‐assisted sol–gel fabricated BGs. Granular size, shape, and porosity have a significant role at the point of contact with cellular membrane. Therefore, we studied the biocompatibility with respect to morphology and porosity of the fabricated BGs. From this study, we observed that the BG prepared using probe sonication method controls the particle size, further it enhances the porosity that altogether improves the biocompatibility. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:143–155, 2020.