Potential usage of biodegradable and biocompatible polymeric nanofibers is the most attention grabbing topic for the drug delivery system. In order to fabricate ultrafine fibers, electrospinning, one of the well-known techniques, has been extensively studied in the literature. In the present study, the objective is to achieve the optimum blend of hydrophobic and hydrophilic polymers to be used as a drug delivery vehicle and also to obtain the optimum amount of doxycycline (DOXH) to reach the optimum release. In this case, the biodegradable and biocompatible synthetic polymers, poly(e-caprolactone) (PCL) and poly(ethylene oxide) (PEO), were blended with different ratios for the production of DOXH-loaded electrospun PCL/PEO membranes using electrospinning technique, which is a novel attempt. The fabricated membranes were subsequently characterized to optimize the blending ratio of polymers by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD) and water contact angle analysis. After the characterization studies, different amounts of DOXH were loaded to the optimized blend of PCL and PEO to investigate the release of DOXH from the membrane used as a drug delivery vehicle. In vitro drug release studies were performed, and in vitro drug release kinetics were assessed to confirm the usage of these nanofiber materials as efficient drug delivery vehicles. The results indicated that 3.5% DOXH-loaded (75:25 w/w) PCL/PEO is the most acceptable membrane to provide prolonged release rather than immediate release of DOXH.