Physical therapy is the predominant treatment of symptoms. Orthopedic shoes and foot surgery can be used to manage foot problems.

Gene-based therapies for patients with HSAN I are not available to date, hence supportive care is the only treatment available for the patients. Ulcero-mutilating complications are the most serious, prominent, and leading diagnostic features in HSAN I. Since the complications mimic foot ulcers caused by diabetic neuropathy, the treatment for foot ulcers and infections can follow the guidelines given for diabetic foot care which starts with early and accurate counseling of patients about risk factors for developing foot ulcerations. Orthopedic care and the use of well fitting shoes without pressure points should also be included. Recently, the treatment of the foot complications has reached an efficient level allowing treatment on an outpatient basis. Early treatment of the foot complications often avoids hospitalization and, in particular, amputations. In sum, the principles of the treatment are removal of pressure to the ulcers, eradication of infection, and specific protective footwear afterwards.

If patients with HSAN I receive appropriate treatment and counseling, the prognosis is good. Early treatment of foot infections may avoid serious complications. Nevertheless, the complications are manageable, thus allowing an acceptable quality of life. The disease progresses slowly and does not influence the life expectancy if signs and symptoms are properly treated.

Often the most important goal for patients with CMT is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy, physical therapy, orthotist, podiatrist and or orthopedic surgeon is recommended. PT typically focuses on muscle strength training, muscle, and ligament stretching while OT can provide education on energy conservation strategies and moderate aerobic exercise in activities of daily living. Physical therapy should be involved in designing an exercise program that fits a person's personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. An orthotist may address gait abnormalities by prescribing the use of ankle-foot orthoses (AFOs). These orthoses help control foot drop and ankle instability and often provide a better sense of balance for patients. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for help in trimming nails or removing calluses that develop on the pads of the feet. A final decision a patient can make is to have surgery. Using a podiatrist or an orthopedic surgeon, patients can choose to stabilize their feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. CMT patients must take extra care to avoid falling because fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen.

The Charcot-Marie-Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states that "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms."

There are also several corrective surgical procedures that can be done to improve physical condition.

There is currently no known pharmacological treatment to hereditary motor and sensory neuropathies. However, the majority of people with these diseases are able to walk and be self-sufficient. Some methods of relief for the disease include physical therapy, stretching, braces, and sometimes orthopedic surgery. Since foot disorders are common with neuropathy disorders precautions must be taken to strengthen these muscles and use preventative care and physical therapy to prevent injury and deformities.

There is no pharmacological treatment for Roussy–Lévy syndrome.

Treatment options focus on palliative care and corrective therapy. Patients tend to benefit greatly from physical therapy (especially water therapy as it does not place excessive pressure on the muscles), while moderate activity is often recommended to maintain movement, flexibility, muscle strength and endurance.

Patients with foot deformities may benefit from corrective surgery, which, however, is usually a last resort. Most such surgeries include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. Recovering from these surgeries is oftentimes long and difficult. Proper foot care including custom-made shoes and leg braces may minimize discomfort and increase function.

While no medicines are reported to treat the disorder, patients are advised to avoid certain medications as they may aggravate the symptoms.

There is no current treatment, however management of hereditary neuropathy with liability to pressure palsy can be done via:

- Occupational therapist

- Ankle/foot orthosis

- Wrist splint (medicine)

- Avoid repetitive movements

Cyclophosphamide is a drug often used in the treatment of lymphomas and works by slowing or stopping cell growth. It also works as an immunosuppressant by decreasing the body’s immune response to various diseases and conditions. This drug has been found to make significant improvements in people with anti-MAG neuropathy by relieving sensory loss and helping to improve quality of life in a few short months. There is, however, a risk of cancer because of this treatment and is therefore not used on a regular basis.

Chlorambucil is a chemotherapy drug normally used to treat leukemia as it is often used as an immunosuppressant drug, and prednisone is a steroid that has also been found to be particularly effective as an immunosuppressant. This combination of drugs has minimal to no benefits in most patients, but a small number do see small improvements such as decreased tremors. This combination has not been very effective in more severe cases, though, and is not considered a long term therapy.

NARP syndrome is not curable. Symptomatic relief is targeted. Antioxidants play a role in improving the oxidative phosphorylation that is otherwise impaired.

Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present.

Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and blood pressure. There are some commonly needed treatments including:

1. Artificial tears: using eye drops containing artificial tear solutions (methylcellulose)

2. Feeding: Maintenance of adequate nutrition, avoidance of aspiration; thickened formula and different shaped nipples are used for baby.

3. Daily chest physiotherapy (nebulization, bronchodilators, and postural drainage): for Chronic lung disease from recurrent aspiration pneumonia

4. Special drug management of autonomic manifestations such as vomiting: intravenous or rectal diazepam (0.2 mg/kg q3h) and rectal chloral hydrate (30 mg/kg q6h)

5. Protecting the child from injury (coping with decreased taste, temperature and pain perception)

6. Combating orthostatic hypotension: hydration, leg exercise, frequent small meals, a high-salt diet, and drugs such as fludrocortisone.

7. Treatment of orthopedic problems (tibial torsion and spinal curvature)

8. Compensating for labile blood pressures

There is no cure for Familial Dysautonomia.

Treatment is dependent upon diagnosis and the stage at which the diagnosis is secured. For toxic and nutritional optic neuropathies, the most important course is to remove the offending agent if possible and to replace the missing nutritional elements, orally, intramuscularly, or intravenously. If treatment is delayed, the injury may be irreversible. The course of treatment varies with the congenital forms of these neuropathies. There are some drug treatments that have shown modest success, such as Idebenone used to treat LOHN. Often treatment is relegated to lifestyle alterations and accommodations and supportive measures.

Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides and open new avenues of therapeutic intervention. Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.

Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

There is currently no cure for FD and death occurs in 50% of the affected individuals by age 30. There are only two treatment centers, one at New York University Hospital and one at the Sheba Medical Center in Israel. One is being planned for the San Francisco area.

The survival rate and quality of life have increased since the mid-1980s mostly due to a greater understanding of the most dangerous symptoms. At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.

A major issue has been aspiration pneumonia, where food or regurgitated stomach content would be aspirated into the lungs causing infections. Fundoplications (by preventing regurgitation) and gastrostomy tubes (to provide nonoral nutrition) have reduced the frequency of hospitalization.

Other issues which can be treated include FD crises, scoliosis, and various eye conditions due to limited or no tears.

An FD crisis is the body's loss of control of various autonomic nervous system functions including blood pressure, heart rate, and body temperature. Both short-term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.

Succinic acid has been used successfully to treat MELAS syndrome, and also Leighs disease. Patients are managed according to what areas of the body are affected at a particular time. Enzymes, amino acids, antioxidants and vitamins have been used.

Also the following supplements may help:

- CoQ10 has been helpful for some MELAS patients. Nicotinamide has been used because complex l accepts electrons from NADH and ultimately transfers electrons to CoQ10.

- Riboflavin has been reported to improve the function of a patient with complex l deficiency and the 3250T-C mutation.

- The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impairment of vasodilation in intracerebral arteries due to nitric oxide depletion.

- There is also a case report where succinate was successfully used to treat uncontrolled convulsions in MELAS patients, although this treatment modality is yet to be thoroughly investigated or widely recommended.

No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include:

- Baclofen – a voluntary muscle relaxant to relax muscles and reduce tone. This can be administered orally or intrathecally. (Studies in HSP )

- Tizanidine – to treat nocturnal or intermittent spasms (studies available )

- Diazepam and clonazepam – to decrease intensity of spasms

- Oxybutynin chloride – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems

- Tolterodine tartate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems

- Botulinum toxin – to reduce muscle overactivity (existing studies for HSP patients)

- Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression

- Physical therapy – to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores.

First-line treatment for CIDP is currently intravenous immunoglobulin (IVIG) and other treatments include corticosteroids (e.g. prednisone), and plasmapheresis (plasma exchange) which may be prescribed alone or in combination with an immunosuppressant drug. Recent controlled studies show subcutaneous immunoglobin (SCIG) appears to be as effective for CIDP treatment as IVIG in most patients, and with fewer systemic side effects.

IVIG and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. IVIG is probably the first-line CIDP treatment, but is extremely expensive. For example, in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $8,000 just for the immunoglobulin—not including other charges such as nurse administration. Gamunex brand IVIG is the only U.S. FDA approved treatment for CIDP, as in 2008 Talecris, the maker of Gamunex, received orphan drug status for this drug for the treatment of CIDP.

Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including rituximab (Rituxan) which targets B cells, and cyclophosphamide, a drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach. Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.

Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In the U.S., these drugs are used as "off-label" treatments for CIDP, meaning that their use here is accepted by the FDA, but that CIDP treatment is not explicitly indicated or approved in the drug literature. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used.

Anti-thymocyte globulin (ATG), an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody.

Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials.

A review of several treatments found that azathioprine, interferon alpha and methotrexate were not effective. Cyclophosphamide and rituximab seem to have some response. Mycophenolate mofetil may be of use in milder cases. Immunoglobulin and steroids are the first line choices for treatment. Rarely bone marrow transplantation has been performed.

Physical therapy and occupational therapy may improve muscle strength, activities of daily living, mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.

Multifocal motor neuropathy is normally treated by receiving intravenous immunoglobulin (IVIG), which can in many cases be highly effective, or immunosuppressive therapy with cyclophosphamide or rituximab. Steroid treatment (prednisone) and plasmapheresis are no longer considered to be useful treatments; prednisone can exacerbate symptoms. IVIg is the primary treatment, with about 80% of patients responding, usually requiring regular infusions at intervals of 1 week to several months. Other treatments are considered in case of lack of response to IVIg, or sometimes because of the high cost of immunoglobulin. Subcutaneous immunoglobulin is under study as a less invasive, more-convenient alternative to IV delivery.

A range of medications that act on the central nervous system has been found to be useful in managing neuropathic pain. Commonly used treatments include tricyclic antidepressants (such as nortriptyline or amitriptyline), the serotonin-norepinephrine reuptake inhibitor (SNRI) medication duloxetine, and antiepileptic therapies such as gabapentin, pregabalin, or sodium valproate. Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.

Symptomatic relief for the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. The evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option. Local anesthesia often is used to counteract the initial discomfort of the capsaicin. Some current research in animal models has shown that depleting neurotrophin-3 may oppose the demyelination present in some peripheral neuropathies by increasing myelin formation.

High-quality evidence supports the use of cannabis for neuropathic pain.

Treatment is based on the underlying cause, if any. Where the likely underlying condition is known, treatment of this condition is indicated treated to reduce progression of the disease and symptoms. For cases without those conditions, there is only symptomatic treatment.

Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of deoxyribonucleotides (dNTPs) in mitochondria.

TCAs include imipramine, amitriptyline, desipramine, and nortriptyline. They are generally regarded as first or second-line treatment for DPN. Of the TCAs, imipramine has been the best studied. These medications are effective at decreasing painful symptoms but suffer from multiple side effects that are dose-dependent. One notable side effect is cardiac toxicity, which can lead to fatal abnormal heart rhythms. Additional common side effects include dry mouth, difficulty sleeping, and sedation. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.

Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties. Opioid medications are recommended as second or third-line treatment for DPN.

Therapy for notalgia paresthetica is directed at controlling symptoms, as no cure exists for the condition. Available treatments include local anesthetics, topical capsaicin, topical corticosteroids, hydroxyzine, oxcarbazepine, palmitoylethanolamide and gabapentin. Paravertebral nerve block and botulinum toxin injections may also be helpful.

Some patients treated with low concentration topical capsaicin reported pain, burning, or tingling sensations with treatment, and symptoms returned within a month of ceasing treatment. Oxcarbazepine was reported to reduce the severity of symptoms in a few cases. One patient has been treated with "paravertebral nerve blocks, with bupivacaine and methylprednisolone acetate injected into the T3–T4 and T5–T6 intervertebral spaces" Hydroxyzine has also been used with considerable success in some cases as long as the pills are used daily.

High concentration topical capsaicin (8%, Qutenza) have been shown to be highly effective in treating neuropathic itch in some patients (including notalgia paresthetica) as well as in a recent proof-of-concept study, but this remains to be confirmed in randomised controlled trials.

Most recently intradermal injections of botulinum toxin type A (Botox) have been tried with some success. Even though botulinum normally wears off in three to six months, the treatment appears to be long term, and it has been theorised that botulinum type A effects lasting change in pain signaling. Unfortunately, repeated injections have been associated with diminished movement ability of the upper back and arms and its recommendation as a treatment has therefore become less popular.

The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well.