This study explored the key active components of Ligusticum chuanxiong and their mechanisms in treating Parkinson's disease (PD) and Alzheimer's disease (AD). Initially, network pharmacology was employed to screen active ingredients and therapeutic targets of L. chuanxiong for PD and AD, constructing a multi-dimensional interaction network of "drug-disease-component-target". Then, an oxidative damage model in human neuroblastoma SH-SY5Y cells was established using 1-methyl-4-phenylpyridinium (MPP⁺) and β-amyloid fragment Aβ_25-35. Cellular viability, oxidative stress markers, and signaling pathway activation were evaluated to investigate the underlying mechanisms. Results revealed myricanone (MyR) as the pivotal active component, exerting neuroprotection by modulating core targets such as glycogen synthase kinase-3β (GSK-3β). MyR significantly alleviated MPP⁺/Aβ_25-35-induced oxidative damage in SH-SY5Y cells, enhanced cell viability, and promoted phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and GSK-3β. These effects were reversed by pathway inhibitors. Collectively, MyR enhanced cellular antioxidant capacity via the PI3K/AKT/GSK-3β signaling axis and ameliorated MPP⁺/Aβ_25-35-induced neuronal oxidative damage, highlighting its potential application for PD/AD drug development.