The therapeutic potential of essential oils is widely recognized since antiquity, due to their antibacterial, antifungal, anti-inflammatory and immuno-modulatory properties. In particular, their physicochemical characteristics, such as lipophilicity and permeation enhancement effect have sparked attention for the development of innovative lipid nanosystems.The present work aimed at developing a differentiated nanostructured lipid carrier (NLC) based formulation for topical application, using the Ridolfia segetum essential oil (REO), isolated by hydrodistillation from this Portuguese aromatic plant, with a dual key function, as active and simultaneously nanostructuring component of the nanoparticles. The incorporation of the essential oil in the solid lipid matrix, followed by the respective hot high-pressure homogenization, led to particles with a size of 143 ± 5 nm, along with a polydispersity index of 0.21, a zeta potential of −16.3 ± 0.6 mV, encapsulation efficacy of ca. 100% and loading capacity of 1.4%. A comprehensive physicochemical characterization of the lipid nanosystem, including morphology, structural, thermal and accelerated stability analysis confirmed its nanostructured nature. REO-NLC was further jellified for designing an appropriate semisolid topical dosage form. In vitro release, permeation and skin retention studies evidenced a sustained release behaviour and a reservoir-like effect, suitable for a prolonged topical delivery. Cytotoxicity studies, performed in fibroblasts and keratinocytes, revealed the biocompatibility of the developed formulations.This work highlights the critical role of REO as a multiaddressable compound, both as active pharmaceutical ingredient and nanostructuring agent, able to tailor the permeation enhancement profile of nanoparticles towards topical delivery purposes and concomitantly presenting a safety profile for cosmetic and/or pharmaceutical purposes.