Tissue engineering has emerged as an effective alternative treatment modality that aims to regenerate damaged tissues instead of replacing them. This study aimed to prepare polycaprolactone (PCL)/zein/bioglass composite scaffolds with high porosity and high interconnectivity for bone tissue engineering applications. PCL, as a synthetic polymer was blended with corn protein (Zein) to fabricate PCL/zein scaffolds. Ananosized bioglass (BG), was also, added to PCL/zein mixture to prepare PCL/zein/BG composite scaffolds using the solvent casting method. Pore size and morphology were investigated using scanning electron microscopy (SEM). The mechanical properties, the porosity and the biodegradation rate of the scaffolds were assessed. Also, the viability and osteogenic differentiation of the mesenchymal stem cells (MSCs) cultured on different PCL scaffolds were evaluated using MTT assay and Alkaline phosphatase activity (ALP) assay, respectively. SEM showed that the fabricated scaffolds had highly porous with a highly interconnected structure. High mechanical properties of about 3.41 MPa and higher degradations rate (42%) were obtained by PCL/Zein/BG composite scaffold compared to the pure PCL scaffold and PCL/Zein scaffold. PCL/Zein/BG composite scaffold was shown to be noncytotoxic and supported mesenchymal stem cell (MSC) attachment and differentiation as indicated by viability assay (MTT) and alkaline phosphatase activity (ALP) assay. The addition of BG nanoparticles into the scaffold improved the mechanical and degradation rate of the hydrophobic polymers. In addition, the BG promoted better cell adhesion, proliferation, and differentiation. Thus, the study showed that the PCL/Zein/BG composite scaffolds are potential candidates for regenerating damaged bone tissues.