© 2016The current research was conducted to propose a nanocomposite material, which could be suitable to be used as a scaffold for bone tissue engineering applications. For this purpose, nanocomposite fibers of gelatin, poly(ε-caprolactone) (PCL), and bioactive glass were successfully fabricated via electrospinning process. In this context, response surface methodology based on a three-level, four-variable Box-Behnken design was adopted as an optimization tool to choose the most appropriate parameter settings to obtain the desired fiber diameter. The investigation, based on a second order polynomial model, focused on the analysis of the effect of both solution and processing parameters on the fiber diameter and its standard deviation. In optimum conditions (bioactive glass content of 7.5% (w/v), applied voltage of 25 kV, tip-to-collector distance of 12.5 cm, and flow rate of 1 mL/h), the fiber diameter was found to be 584 ± 337 nm which was in good agreement with the predicted value by the developed models (523 ± 290 nm). Analytical tools such as scanning electron microscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy, and differential thermal analyzer were used for further evaluation of the optimized nanocomposite mat. The overall results showed that nanocomposite scaffolds could be promising candidates for tissue engineering applications.