The ancestral Mapuche people of southern Chile have a rich ethnobotanical tradition based on knowledge of the use of medicinal plants for health care and spiritual balance. Currently, oxidative stress is recognized as one of the mechanisms involved in the pathophysiology of neurodegenerative diseases such as Alzheimer's and Parkinson's, which is why research in the field of medicinal chemistry has focused on finding natural compounds from species with high neuroprotective potential. This paper presents a systematic review with an ethnopharmacological focus on native Chilean plants used by the Mapuche community to treat symptoms compatible with neurodegenerative processes. Based on semi-structured interviews and a review of scientific databases, the species Aristotelia chilensis, Buddleja globosa, Fuchsia magellanica, Drymis winteri, Peumus boldus, and Ugni molinae were highlighted. These species have been evaluated through the metabolomic characterization of polar and aqueous extracts with high concentrations of polyphenolic compounds and have demonstrated strong antioxidant effects and inhibition of the intracellular production of reactive oxygen species (ROS). Likewise, Adiantum capillus-veneris, Baccharis tola, Berberis darwinii, Crytocarpa alba, Gevuina avellana, Greigia sphacelata, Lapageria rosea, Laurelia sempervirens, Lophosoria quadripinnata, Otholobium glandulosum, and Weinmannia trichosperma are also reported to have neuroprotective potential. Infusions and decoctions are the main forms of preparation in communities, which is directly related to the study methodologies for their chemical validation. This study contributes to the assessment and relevance of the Chilean Pharmacopoeia and the importance of preserving traditional knowledge. Ethnobotany is a source of inspiration and biomedical research in the search for therapeutic alternatives for diseases related to neuronal damage.