Cutaneous drug delivery provides a painless route of drug administration while avoiding first-pass metabolism and many side effects as the drug can be delivered locally rather than entering the systemic circulation. However, overcoming the skin’s outermost barrier, the stratum corneum (SC), remains a significant challenge [1]. To enhance skin permeability, ionic liquids (ILs) have emerged as promising carriers for the cutaneous delivery of active pharmaceutical ingredients (APIs) due to their tunable physicochemical properties and their ability to solubilize hydrophobic compounds while effectively interacting with the SC. This study investigates the potential of the biocompatible ionic liquid choline geranate (CAGE) at a 1:2 choline-to-geranic acid molar ratio in transdermal drug delivery systems (TDDS), focusing on the relationship between its biophysical characteristics and interactions with the skin barrier.