In pursuing sustainable health solutions and growing demand for neuroprotective interventions, the industry demands alternative green extraction technologies to valorize agri-food by-products. This study aimed to develop an optimized supercritical carbon dioxide extraction to isolate sesame meal's functional compound (lignans) and assess their neuroprotective effects. Extraction was performed at various pressures (2-4 kpsi), temperatures (40-60 °C), co-solvent concentrations (2-25 mol% ethanol), and CO