<p>Oxidative stress in neuronal cells plays a crucial role in the onset and progression of Alzheimer's disease, making the protection of cells from oxidative damage by natural products a topic of significant interest. This study aimed to investigate the protective effects of ginkgolide A against hydrogen peroxide (H₂O₂)-induced oxidative damage in human neuroblastoma SH-SY5Y cells and elucidate its underlying mechanisms. Our findings demonstrated that ginkgolide A, at concentrations ranging from 5 to 40&#xa0;µM, exhibited no cytotoxic effects on SH-SY5Y cells. In contrast to the H₂O₂-treated group, ginkgolide A at concentrations of 5 to 20&#xa0;µM concentration-dependently enhanced cell viability, inhibited apoptosis, and increased mitochondrial membrane potential. Furthermore, ginkgolide A elevated intracellular levels of glutathione and antioxidant enzymes such as superoxide dismutase and catalase, while reducing malondialdehyde production, thus mitigating oxidative damage. Mechanistic studies revealed that ginkgolide A upregulated the mRNA levels and protein expression of Nrf2, HO-1 and NQO-1, suggesting its potential to activate the Nrf2 signaling pathway and alleviate oxidative stress. Additionally, ginkgolide A decreased the phosphorylation levels of ERK1/2 and JNK, indicating its involvement in activating the Nrf2 pathway possibly via modulation of MAPK signaling. In summary, ginkgolide A effectively mitigated oxidative damage in SH-SY5Y cells, exerting neuroprotective effects and offering promise as a lead compound for Alzheimer's disease therapy.</p> Graphical Abstract <p></p>