There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. Liver transplants may benefit people with liver involvement.

DGUOK, POLG, and MPV17 related forms result in defects to the liver. Liver dysfunction is progressive in the majority of individuals with both forms of DGUOK-related MDS and is the most common cause of death. For children with the multi-organ form, liver transplantation provides no survival benefit.

Liver disease typically progresses to liver failure in affected children with MPV17-related MDS and liver transplantation remains the only treatment option for liver failure. Approximately half of affected children reported did not undergo liver transplantation and died because of progressive liver failure – the majority during infancy or early childhood. A few children were reported to survive without liver transplantation.

For most balance and gait disorders, some form of displacement exercise is thought helpful (for example walking, jogging, or bicycling but not on a treadmill or stationary bicycle). This has not been well-studied in MdDS. Medications that suppress the nerves and brain circuits involved in balance (for example, the benzodiazepine clonazepam) have been noted to help and can lower symptoms, but it is not a cure. It is not known whether medication that suppress symptoms prolongs symptom duration or not. Vestibular therapy has not proved to be effective in treating MdDS.

Additional research is being undertaken into the neurological nature of this syndrome through imaging studies. The disorder remains incurable and permanent if the symptoms do not remit in a short period of time.

At least one clinical trial on readaptation of the vestibulo-ocular reflex undertaken by Dr Mingjia Dai from Mount Sinai Hospital in New York City has produced results for a significant percentage of patients who have participated in the program.

Dai has developed an intervention that provided improvement in symptoms for 70% of the patients in the clinical trial phase. The protocol involves a physical manipulation of the patient intended to readapt the vestibulo-ocular reflex. While the program is no longer in the research phase, Dai continues to accept patients. According to Dai, "success" is measured as a 50% reduction of symptoms.

Recent research reveals a very small percentage of MdDS cases may be related to optokinetic nystagmus (OKN).