The development of biomimetic scaffolds that can promote osteogenic induction and vascularization is of great importance for the repair of large bone defects. In the present study, inorganic bioactive glass (BG) and organic polycaprolactone (PCL) are effectively combined by electrospinning and electrospray techniques to construct three-dimensional (3D) BG/PCL microfibrous spheres for the repair of bulk bone defects. The hybrid fibers, as well as the as-obtained 3D structure, can mimic the composition and architecture of native bone tissues. Furthermore, the BG/PCL microfibrous spheres show excellent biocompatibility and provide sufficient space and attachment sites for cell growth. The osteogenic differentiation of bone mesenchymal stem cells is also effectively facilitated when cultured on such hybrid microfibrous spheres. In vivo investigation utilizing rat femoral condyle bone defect models demonstrates that the BG/PCL microfibrous spheres loaded with bone mesenchymal stem cells can induce angiogenesis and promote the upregulation of bone-related protein expression, thus effectively facilitating bone regeneration at the defect site. The collective findings indicate that such BG/PCL hybrid microfibrous spheres have the potential to be effective carriers of stem cells. The microfibrous spheres loaded with stem cells have promising potential to be utilized as implantable biomaterials for the repair of bone defects.