The key to treating cholera lies in preventing dehydration by replacing the fluids and electrolytes lost through diarrhea and vomiting. The discovery that rehydration can be accomplished orally revolutionized the treatment of cholera and other, similar diseases by making this simple, cost-effective treatment widely available throughout the world. The World Health Organization has developed an inexpensive oral replacement fluid containing appropriate amounts of water, sugar, and salts that is used worldwide. In cases of severe dehydration, replacement fluids must be given intravenously. Patients should be encouraged to drink when they can keep liquids down and eat when their appetite returns. Recovery generally takes three to six days.

Adults may be given the antibiotic tetracycline to shorten the duration of the illness and reduce fluid loss. The World Health Organization recommends this antibiotic treatment only in cases of severe dehydration. If antibiotics are overused, the cholera bacteria organism may become resistant to the drug, making the antibiotic ineffective in treating even severe cases of cholera. Tetracycline is not given to children whose permanent teeth have not come in because it can cause the teeth to become permanently discolored.

Other antibiotics that may be given to speed up the clearance of V. cholerae from the body include ciprofloxacin and erythromycin.

A possible complementary or alternative treatment for fluid loss caused by cholera is a plant-derived compound, an extract made from the tree bark of Croton lechleri, the Sangre de grado tree found in the South American rain forest. Researchers at a hospital research institute in California report that the extract appears to work by preventing the loss of chloride and other electrolytes from the body.