Sesamum eriocarpum was a popular plant among the Khoi and San people of southern Africa. It contains saponins, which are glycosides with a unique foaming characteristic. When the flowers are soaked in water, they produce a mucilaginous substance that was used as soap and shampoo. It was also used by Khoi and San women for tradition foot spas. They would soak the flowers in calabashes, immersing their feet in them for some time. Intekelane was also used for hunting. The dried roots were crushed together with the roasted seed pods of Snake Bean, Bobgunnia madagascariensis (= Swartzia madagascariensis), to make a poisonous substance that was applied to arrows before a hunting trip.

Sesamum eriocarpum is also known for its antibacterial and anti-inflammatory properties. In Botswana, the roots are boiled and taken orally to heal sexually transmitted diseases. During childbirth, an infusion of the whole plant is taken orally and inserted into the vagina to dilate the birth canal. An infusion of the whole plant can be taken orally to cause an abortion. Powdered roots can be mixed with porridge to ease abdominal pains. An infusion of the leaves is also used as body wash to treat measles in children.

In Namibia, the roots are dried, powdered and prepared into a decoction for the treatment of malaria. Plants should be taken in small quantities, as large doses often cause toxicity in patients.

In South Africa, the Venda people of Limpopo Province consume the leaves as a vegetable. Indigenous farmers also use the plant for treating wounds and retained placentas in livestock.