Lipid-based nanocarriers are attractive materials for food and pharmaceutical industries. In particular, phytosomes are platforms to target bioactive phenolics for central nervous system and to modulate pathophysiological processes underlying major chronic disorders. HPLC-DAD profiling of pennyroyal (Mentha pulegium L.) aqueous extract led to the determination of fifteen phenolic compounds (84.00 ± 4.28 mg/g lyophilized extract), of which rosmarinic acid was the major representative. In cell-free assays, the extract displayed a strong inhibitory effect against monoamine oxidase-A (hMAO-A) (IC 50 = 20.11 ± 0.86 μg/mL total phenolics). Pennyroyal phytosomes, prepared with lipids extracted from egg yolks, presented a mean vesicle diameter <200 nm and a negative surface charge (Zeta potential = −15.84 ± 2.32). Their high entrapment efficiency (75.05 ± 6.27%) resulted from well-defined phenolic-phospholipid interactions. In human neuroblastoma SH-SY5Y cells, phytosomes decreased MAO-A activity (48.24 ± 9.02%), highlighting their potential as a nutraceutical nootropic strategy to counteract several neurodegenerative disorders.