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Oxidative stress (OS) arising from tissue redox imbalance, critically contributes to the development of neurodegenerative disorders. Thus, natural compounds, owing to their antioxidant properties, have promising therapeutic potential. <i>Pres phytum</i> (PRES) is a nutraceutical product composed of leaves- and flowers-extracts of <i>Olea europaea</i> L. and <i>Hibiscus sabdariffa</i> L., respectively, the composition of which has been characterized by HPLC coupled to a UV-Vis and QqQ-Ms detector. As PRES possess antioxidant, antiapoptotic and anti-inflammatory properties, the aim of this study was to assess its neuroprotective effects in human neuroblastoma SH-SY5Y cells and in rat brain slices subjected to OS. PRES (1–50 µg/mL) reverted the decrease in viability as well as the increase in sub-diploid-, DAPI-and annexin V-positive-cells, reduced ROS formation, recovered the mitochondrial potential and caspase-3 and 9 activity changes caused by OS. PRES (50–100 µg/mL) neuroprotective effects occurred also in rat brain slices subjected to H₂O₂ challenge. Finally, as the neuroprotective potential of PRES is strictly related to its penetration into the brain and a relatively good pharmacokinetic profile, an in-silico prediction of its components drug-like properties was carried out. The present results suggest the possibility of PRES as a nutraceutical, which could help in preventing neurodegenerative diseases.