To systematically review evidence on the therapeutic potential and underlying mechanisms of nanoparticle-based antioxidant formulations in reducing oxidative stress and promoting neuroprotection across neurodegenerative diseases.

Oxidative stress is a fundamental factor in neuronal injury associated with Alzheimer’s disease, Parkinson’s disease, and related neurodegenerative disorders. Traditional antioxidant therapies have shown limited efficacy due to poor bioavailability, chemical instability, and inadequate passage through the blood–brain barrier. Engineered nanoparticle delivery systems may help overcome these barriers by improving solubility, prolonging drug release, and facilitating targeted deposit within neural tissue.

This systematic review follows the PRISMA 2020 framework. Electronic databases including PubMed, Scopus, and ScienceDirect were searched for studies published between January 2010 and June 2025 that evaluated nanoparticle-based antioxidants in preclinical or clinical models of neurodegeneration. Studies were included if they reported quantitative outcomes related to oxidative markers, neuronal survival, or functional recovery. Two independent reviewers screened and extracted data on nanoparticle composition, mechanism of antioxidant action, and efficacy outcomes. Risk-of-bias assessment and data synthesis are ongoing.

Current evidence supports that nanoparticle-based antioxidant delivery systems enhance bioavailability and demonstrate promising neuroprotective effects across multiple neurodegenerative models. Larger, standardized clinical trials are warranted to establish safety and translational applicability.