Enteroviral infections in immunocompetent individuals heal spontaneously within 7-10 days; therefore, the main goal of treatment is symptomatic relief.
Neonates show a wide spectrum of signs and symptoms, which range from a nonspecific febrile illness to potentially fatal multisystem disease. 
Adequate hydration and antipyretics, such as acetaminophen, are helpful.
Some anecdotal evidence suggests that prophylactic immunoglobulin can mitigate disease severity in some exposed neonates. Immunoglobulin has also been used for the treatment of symptomatic infants with enterovirus infection. 
This is another antiviral drug that has demonstrated efficacy against enteroviruses. It is a broad-spectrum antiviral drug that blocks enteroviral attachment to cellular receptors. [38, 39, 40] Pleconaril therapy is prescribed for the treatment of severe neonatal enteroviral sepsis. 
A novel class of capsid binder, pyridyl imidazolidinone can inhibit enterovirus 71. 
Mouth rinses with topical anesthetics (eg, lidocaine 2%) or antihistamines (eg, diphenhydramine hydrochloride) may relieve oral pain. 
Acyclovir was used in an open clinical trial involving 13 patients with hand-foot-and-mouth disease (HFMD). Involution of oral lesions occurred within 24 hours of the start of therapy. The mechanism of action was unknown; to the authors’ knowledge, no other series results have been published.
Allopurinol mouthwashes (3 mg/mL) are reported to accelerate the resolution of oral lesions.