Investigation of novel biomaterials for bone regeneration is based on the development of scaffolds that exhibit bone-bonding ability, biocompatibility, and sufficient mechanical strength. In this study, using novel poly (ε-caprolactone)/bioactive glass (PCL/BG) hybrids with different organic/inorganic ratios, the effects of BG contents on the in vitro bone-like hydroxyapatite (HA) formation, mechanical properties, and biocompatibility were investigated. Rapid precipitation of HA on the PCL/BG hybrid surfaces were observed after incubating in simulated body fluid (SBF) for only 6 h, as confirmed by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), and inductively coupled plasma atomic emission spectroscopy (ICPS). The ICPS elemental analysis results were further analyzed in terms of the Ca(2+) and PO4(3-) which were consumed to form the apatite layer. The results revealed that the rate and total amount of HA deposition decreased with an increase in PCL content. The compressive modulus and strength of the PCL/BG hybrids increased with the decrease in PCL content. The highest values were achieved at the lowest PCL content (10 wt %) and were around, 90 MPa and 1.4 GPa, respectively. To evaluate the cytotoxicity of PCL/BG bioactive hybrids, MC3T3-E1 osteoblast-like cells were cultured for up to 72 h. Our data indicated that whereas initial cell attachment was marginally lower than the control tissue culture poly styrene (TCPS) surface, the hybrid materials promoted cell growth in a time-dependent manner. Cell viability within the different PCL/BG hybrid samples appeared to be influenced by compositional differences whereby higher PCL contents correlated with slight reduction in cell viability. Taken together, this study adds important new information to our knowledge on hydroxyapatite formation, mechanical properties, and cytotoxic effects of PCL/BG hybrids prepared by the sol-gel process using a tertiary glass composition and may have considerable potential for bone tissue regeneration applications.