There is no effective treatment or antidote for ciguatera poisoning. The mainstay of treatment is supportive care. There is some evidence that calcium channel blockers like nifedipine and verapamil are effective in treating some of the symptoms that remain after the initial sickness passes, such as poor circulation and shooting pains through the chest. These symptoms are due to the cramping of arterial walls caused by maitotoxin Ciguatoxin lowers the threshold for opening voltage-gated sodium channels in synapses of the nervous system. Opening a sodium channel causes depolarization, which could sequentially cause paralysis, heart contraction, and changing the senses of hot and cold. Some medications such as amitriptyline may reduce some symptoms, such as fatigue and paresthesia, although benefit does not occur in every case.

Mannitol was once used for poisoning after one study reported symptom reversal. Follow-up studies in animals and case reports in humans also found benefit from mannitol. However, a randomized, double-blind clinical trial found no difference between mannitol and normal saline, and based on this result, mannitol is no longer recommended.

Long term management of chronic Ciguatera includes avoiding trigger food and environmental triggers, and managing symptoms with medications and or lifestyle.

Caution may be needed with anesthesia and should be discussed with your healthcare providers.

Various Caribbean folk and ritualistic treatments originated in Cuba and nearby islands. The most common old-time remedy involves bed rest subsequent to a guanabana juice enema. Other folk treatments range from directly porting and bleeding the gastrointestinal tract to "cleansing" the diseased with a dove during a Santería ritual. In Puerto Rico, natives drink a tea made from mangrove buttons, purportedly high in B vitamins, to flush the toxic symptoms from the system. There has never been a funded study of these treatments.

An account of ciguatera poisoning from a linguistics researcher living on Malakula island, Vanuatu, indicates the local treatment: "We had to go with what local people told us: avoid salt and any seafood. Eat sugary foods. And they gave us a tea made from the roots of ferns growing on tree trunks. I don't know if any of that helped, but after a few weeks, the symptoms faded away."

Senescent leaves of "Heliotropium foertherianum" (Boraginaceae), also known as octopus bush, a plant used in many Pacific islands as a traditional medicine to treat ciguatera fish poisoning, contain rosmarinic acid and derivatives, which are known for their antiviral, antibacterial, antioxidant and anti-inflammatory properties. Rosmarinic acid may remove the ciguatoxins from their sites of action, as well as being an anti-inflammatory.

Treatment is in the form of supportive care. If there is light-headedness, the victim should lie with feet partly elevated. If there is severe wheezing, then intramuscular epinephrine should be given, 0.5–1 ml at dilution of 1/1000 (standard medical emergency kit). An intravenous antihistamine like diphenhydramine should be given if needed.

Prevention is mainly the role of the state, through the definition of strict rules of hygiene and a public services of veterinary surveying of animal products in the food chain, from farming to the transformation industry and delivery (shops and restaurants). This regulation includes:

- traceability: in a final product, it must be possible to know the origin of the ingredients (originating farm, identification of the harvesting or of the animal) and where and when it was processed; the origin of the illness can thus be tracked and solved (and possibly penalized), and the final products can be removed from the sale if a problem is detected;

- enforcement of hygiene procedures such as HACCP and the "cold chain";

- power of control and of law enforcement of veterinarians.

In August 2006, the United States Food and Drug Administration approved Phage therapy which involves spraying meat with viruses that infect bacteria, and thus preventing infection. This has raised concerns, because without mandatory labelling consumers would not be aware that meat and poultry products have been treated with the spray.

At home, prevention mainly consists of good food safety practices. Many forms of bacterial poisoning can be prevented by cooking it sufficiently, and either eating it quickly or refrigerating it effectively. Many toxins, however, are not destroyed by heat treatment.

Techniques that help prevent food borne illness in the kitchen are hand washing, rinsing produce, preventing cross-contamination, proper storage, and maintaining cooking temperatures. In general, freezing or refrigerating prevents virtually all bacteria from growing, and heating food sufficiently kills parasites, viruses, and most bacteria. Bacteria grow most rapidly at the range of temperatures between , called the "danger zone". Storing food below or above the "danger zone" can effectively limit the production of toxins. For storing leftovers, the food must be put in shallow containers

for quick cooling and must be refrigerated within two hours. When food is reheated, it must reach an internal temperature of or until hot or steaming to kill bacteria.

Unlike many types of food poisoning, scombroid form is not brought about by ingestion of a pathogen. Histidine is an amino acid that exists naturally in many types of food (including fish) and at temperatures above 16 °C/60 °F it is converted to the biogenic amine histamine via the enzyme histidine decarboxylase produced by symbiotic bacteria such as "Morganella morganii" (this is one reason why fish should be stored in the freezer). Histamine is not destroyed by normal cooking temperatures, so even properly cooked fish can still result in poisoning. Histamine is the main natural chemical responsible for true allergic reactions, so the symptoms produced are almost identical to a food allergy.

Several foods can naturally contain toxins, many of which are not produced by bacteria. Plants in particular may be toxic; animals which are naturally poisonous to eat are rare. In evolutionary terms, animals can escape being eaten by fleeing; plants can use only passive defenses such as poisons and distasteful substances, for example capsaicin in chili peppers and pungent sulfur compounds in garlic and onions. Most animal poisons are not synthesised by the animal, but acquired by eating poisonous plants to which the animal is immune, or by bacterial action.

- Alkaloids

- Ciguatera poisoning

- Grayanotoxin (honey intoxication)

- Mushroom toxins

- Phytohaemagglutinin (red kidney bean poisoning; destroyed by boiling)

- Pyrrolizidine alkaloids

- Shellfish toxin, including paralytic shellfish poisoning, diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning and ciguatera fish poisoning

- Scombrotoxin

- Tetrodotoxin (fugu fish poisoning)

Some plants contain substances which are toxic in large doses, but have therapeutic properties in appropriate dosages.

- Foxglove contains cardiac glycosides.

- Poisonous hemlock (conium) has medicinal uses.

Antiemetic medications may be helpful for treating vomiting in children. Ondansetron has some utility, with a single dose being associated with less need for intravenous fluids, fewer hospitalizations, and decreased vomiting. Metoclopramide might also be helpful. However, the use of ondansetron might possibly be linked to an increased rate of return to hospital in children. The intravenous preparation of ondansetron may be given orally if clinical judgment warrants. Dimenhydrinate, while reducing vomiting, does not appear to have a significant clinical benefit.

Antimotility medication has a theoretical risk of causing complications, and although clinical experience has shown this to be unlikely, these drugs are discouraged in people with bloody diarrhea or diarrhea that is complicated by fever. Loperamide, an opioid analogue, is commonly used for the symptomatic treatment of diarrhea. Loperamide is not recommended in children, however, as it may cross the immature blood–brain barrier and cause toxicity. Bismuth subsalicylate, an insoluble complex of trivalent bismuth and salicylate, can be used in mild to moderate cases, but salicylate toxicity is theoretically possible.