 Nanosyme-integrated metal-organic frameworks with excellent antioxidant activity and chiral-dependent BBB-transendocytosis are reported as promising anti-neuro-inflammatory agents for the treatment of Parkinson's disease. Symmet DZIF shows superior therapeutic efficacy in reducing behavioral disorders and pathological changes due to higher accumulation in the brains of male PD mouse models, longer plasma residence time, and more pathways to traverse BBB including clathrin-mediated and cavioli-mediated endocytosis. Bioinformatics and biochemical analyses suggest that Symmet DZIF inhibits neuro-inflammation-induced apoptosis and ferreptosis in damaged neurons, providing possibilities for devising anti-PD drugs. This article was authored by Wei Jiang, Qing Li, Ruofei Zhong, and others.