Herbalists use sassafras for a variety of medicinal uses. It is said to have value as a stimulant, pain reliever, astringent, and treatment for rheumatism. Skin eruptions may be bathed in an infusion from the leaves. Sassafras tonic has been used as a treatment for syphilis since the early 1600's.

It is reported that chewing on the bark may help break the tobacco habit; however, ingestion of sassafras may cause vomiting and can be toxic if taken in large doses. Medicinal use of sassafras has declined in recent years because of the possibility that it may contain carcinogens (cancer-causing agents).

In addition to medicinal uses, sassafras wood, bark, and roots produce an extract (oil of sassafras) that is useful in flavorings, or in perfumes and scented soaps. A yellow dye is also extracted from the trees. The crushed leaves were used by colonists to thicken soups and stews. Sassafras wood is very durable, and is used to make buckets, barrels, poles, posts, and crossties. It is also used in interior cabinetry.