By Mayo Clinic Staff. There's no specific treatment for hand-foot-and-mouth disease. Signs and symptoms of hand-foot-and-mouth disease usually clear up in seven to 10 days. A topical oral anesthetic may help relieve the pain of mouth sores. Over-the-counter pain medications other than aspirin, such as acetaminophen (Tylenol, others) or ibuprofen (Advil, Motrin IB, others) may help relieve general discomfort.