Display omitted •Nanofibers with loaded ionic liquid were successfully produced.•Rised IL content reduce viscosity and increase conductivity electrospinning solution.•PEO-IL nanofibers' average diameter decreased with the increased IL content.•Thicker nanofibers were obtained with a higher molecular weight polymer.•Abcence of hydrogen bonds between ILs and PEO in electrospun nanofibers. Keeping up with cutting edge research in the field of drug delivery, the overall goal of this study was to develop innovative electrospun nanofibers loaded with ionic liquids (ILs) as active pharmaceutical ingredients (APIs). For the first time, a novel approach was examined by combining biocompatible polymer, poly (ethylene oxide) (PEO), and pharmaceutical ILs in an electrospinning process to develop nanofibers with high drug loading (up to 47%). Firstly, two well-known local anaesthetic drugs, lidocaine and procaine, were modified into ILs with the salicylate, forming lidocaine salicylate and procaine salicylate. Its dual-functional nature and increased water solubility for 4- to 10-fold depending on the drug used contribute to overcoming current hurdles encountered by APIs such as poor solubility, low bioavailability, and polymorphism of the solid-state. Nanofibers were formulated using solutions tested for density, viscosity, electrical conductivity, and small-angle X-ray scattering by varying PEO molecular weight and the PEO to IL mass ratio. Scanning electron microscopy showed the surface morphology of the obtained nanofibers, while Fourier transform infrared spectroscopy and differential scanning calorimetry confirmed IL in the nanofibers in an amorphous state. Thus, nanofibers with incorporated IL represent well-known drugs in the new form and a novel dermal application delivery system.