© 2017, Springer-Verlag GmbH Germany, part of Springer Nature.Novel core–shell nanofiber structures loaded by an essential oil using chitosan (CH) as a polymer have been successfully produced via the simple and effective production method of coaxial electrospinning. For this purpose, origanum minutiflorum (OM) oil was incorporated into the nanofibers. A blended form of the nanofibers (B–OM) was obtained by simply mixing OM with CH polymer solution, then this blended form was loaded separately into the core (C–OM) and the shell (S–OM) layers to obtain different composite core–shell nanofiber structures. The structures of the core and shell layers were investigated by TEM analysis. Furthermore, water contact angle analysis confirmed composition of the shell layer of each nanofiber type of B–OM, S–OM, C–OM, and differentiated it from the monolithic nanofiber of CH. The SEM images displayed the average diameter of the C–OM as 291 ± 10, while S–OM nanofibers demonstrated 284 ± 12 nm. The S–OM composite nanofibers showed the highest antibacterial activity during 24 h of the testing time. The nanofiber mats of B–OM and S–OM showed initial burst release with different profiles over an extended 7-day period of time after investigation with an in vitro drug release test. Moreover, C–OM nanofibers demonstrated prolonged time for in vitro drug release behavior with the initial burst profile at 8 h, then the release profile was relatively slow and sustained for about 7 days. The OM oil included nanofiber mats with different core–shell and blended morphologies that can hold a great promise for wound healing, antibacterial, and biomedical applications due to the controlled and tunable drug release and antibacterial activities. Another important advantage of our method over the traditional techniques is being eco-friendly, since it uses natural compound and natural polymer with controllable gas permeability of the nanofiber porous structure.