Delivering hydrophobic drug within hydrophilic polymer matrix as carrier is usually a challenge. Here we report the synthesis of gelatin nanofibers by electrospinning, followed by testing them as a potential carrier for oral drug delivery system for a model hydrophobic drug, piperine. Electrospun gelatin nanofibers were crosslinked by exposing to saturated glutaraldehyde (GTA) vapor, to improve their water resistive properties. An exposure of only 6. min was not only adequate to control the early degradation with intact fiber morphology, but also significantly marginalized any adverse effects associated with the use of GTA. Scanning electron microscopy imaging, Fourier transform infrared spectroscopy and thermogravimetric analysis were done to study nanofiber morphology, stability of drug and effect of crosslinking. The pH of release medium was also varied as per the gastrointestinal tract for in-vitro drug release study. Results illustrate good compatibility of hydrophobic drug in gelatin nanofibers with promising controlled drug release patterns by varying crosslinking time and pH of release medium. © 2015 Elsevier B.V.