Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with brain damage induced by β-amyloid and tau accumulation. One of the hallmarks of amyloidogenesis, is the aggregation of amyloid proteins into a specific cross-β sheet structure, which alters their biological activity thereby affecting neuronal connectivity and function. Despite significant progress in the management of AD over the recent years, the early diagnostic and treatment options still remain limited. Recently, great attention has been focused on the advancement of therapeutic strategies exploiting the antioxidant properties of naturally occurring compounds. Flavonoids, a major class of phytochemicals, have been found to possess a multiple range of health promoting effects, including neuroprotection. Chrysin (ChR) is a flavonoid of the flavone class with potent neuroprotective and anti-inflammatory activity. In addition, ChR improves cognitive decline by exerting anti-amyloidogenic and neurotrophic effects. Magnetic nanoparticles allow binding of drugs by entrapment on the particles, adsorption, or covalent attachment. In our study, well characterized ChR-loaded magnetic PEGylated silica nanospheres (MChRPNPs) were employed with potential enhanced protective characteristics against amyloid induced oxidative stress. The interactions of MChRPNPs with β-amyloid were demonstrated in rat hippocampal cell cultures. Overall, the findings regarding the biological activity profile of MChRPNPs in a cellular amyloidogenic environment suggest an improved specificity of antioxidant properties counteracting amyloid mediated oxidative stress reactivity.