Zanthoxylum schinifolium (Siebold & Zucc.) is a folk and popular aromatic plant due to its exceptional biological properties. However, its use is limited in the industry due to its essential oil volatility and rapid degradation. In the current work, nanotechnology was applied to optimize physicochemical characteristics, long-term stability, and antioxidant performance of essential oil isolated from Z. schinifolium (ZSEO). Chromatographic analysis of isolated sonochemical ZSEO showed that linalool (57.54 %) is the main component. A distinctive and stable ZSEO nanoemulsion (ZSEO-NE) was successfully fabricated through designing an energy-saving, efficient, and applicable approach. response surface methodology (RSM) based on Box–Behnken design was the approach used for optimization processes. Double homogenization processes were successfully applied based on the sonochemical cavitation phenomenon, together with a high-pressure micro-fluidization homogenizer to form nano-scale size droplets. Octenyl succinic modified starch (OSA-MS) was the wall material and surfactant used. Tween-80 was used as a non-ionic surfactant. refined, bleached, and deodorized sunflower oil was served as a carrier material. dynamic light scattering (DLS) technique was used to analyze the droplet hydrodynamic diameter (DHD) (nm), polydispersity index (PdI), ζ-potential (mV). Optical microscopy, Fluorescence microscopy, and confocal laser scanning microscopy (CLSM) were applied for microstructure studies of ZSEO-NE. Gravitational separation and stability of physicochemical properties during long-term storage were evaluated. The optimum values of the mean DHD, PdI, and ζ-potential of ZSEO-NE ranged from 128.8 nm, 141.0, and -44.0 mV, respectively. The findings of the RSM analysis showed considerable agreement between the predictive values and the actual values, in a clear indication that the quadratic model obtained from the BBD matrix covers the experimental range of the current study. Treatment of ZSEO-NE showed maximum stability and less susceptible to droplet aggregation without noticeable separation between aqueous and organic phases during long-term storage.