Ten traditional herbal extracts effective against diarrhea, infectious diseases, and bacterial activity were selected and analyzed for Peyer’s patch cell-mediated intestinal immunomodulatory activity in vitro and in vivo. Among the 10 herbal extracts, Zingiber officinale Rosc. (ZO) extract induced the highest secretion of immunoglobulin A (IgA) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cells of Peyer’s patches. Furthermore, animal experiments showed that IA production was enhanced with the oral administration of ZO extract (100 mg/kg and 300 mg/kg) for 10 days. In addition, 6-, 8-, 10-gingerol, and 6-, 8-, 10-shogaol, the six major index compounds of ZO extract, were analyzed using HPLC. Our study findings confirm the intestinal immunomodulatory activity of ZO extract and lay a strong foundation for future analytical studies aimed at determining the active components of ZO extracts.