The yellow inner bark and roots contain a bitter principle; the roots have been used medicinally and in making yellow dye. Bundles of yellowroot are widely sold in Alabama and Georgia for treatment of gastrointestinal disorders and fever blisters (R. D. Whetstone, pers. comm.).
Native Americans used Xanthorhiza simplicissima medicinally to treat ulcerated stomachs, colds, jaundice, piles, sore mouth, sore throat, cancer, and cramps, and as a blood tonic (D. E. Moerman 1986).