Hand-foot-and-mouth disease is a self-limiting infection that is typically benign in nature. For this reason, it is treated symptomatically and tends to resolve within 7 days of presentation. Individuals with painful oral lesions may use saltwater rinses, viscous lidocaine mouthwash, and acetaminophen to help control any discomfort. Exposure to the virus does provides immunity but does not prevent future infection by a different viral strain. There are reports of treatment with corticosteroids, intravenous immunoglobulins, and antiviral medications but nothing has been proven to be highly effective thus far. Children diagnosed with a suspected enterovirus 71 infection should be hospitalized immediately and treated accordingly to prevent any central nervous system or cardiac involvement.

Due to the highly contagious nature of the disease, frequent hand washing and washing of soiled items is strongly recommended to decrease the spread of this disease. Children with fever, weeping lesions, or those that are actively drooling should be kept from school, day care, or other children. Pregnant women who contract the disease should be seen by an obstetrician who deals with high-risk pregnancies.