Objective This study aims to investigate the mechanism of grape seed oligomeric procyanidins (GPC) in the treatment of experimental autoimmune encephalomyelitis (EAE) mice, providing pharmacodynamic materials for drug development in the treatment of multiple sclerosis (MS). Methods The constituents which have nerve protective effect in GPC were collected through literature retrieval. We used PharmMapper and STITCH database to predict drug targets, GeneCards and OMIM database to predict MS-related genes. Targets of GPC treating MS were obtained from intersected targets between drug and disease. The GO functional enrichment and KEGG pathway enrichment analysis were performed by DAVID database. EAE mouse model was used to study the therapeutic mechanism of GPC. Results Forty-two targets were discovered to be related to the process of GPC treating MS. KEGG enriched a total of 32 pathways. The pharmacological experiment showed that GPC improved the clinical symptoms of EAE mice, inhibited the expression of indicators of oxidative stress and inflammatory response in CNS, and decreased the expression of P-Akt, P-ERK, and P-JNK. Conclusion The therapeutic effect of GPC in EAE mice is associated with the suppression of MAPK and PI3K-Akt signaling pathways, providing a theoretical basis for the application of GPC inMS.