Chloride (Cl)-depletion alkalosis (CDA) develops due to the loss of Cl-rich body fluid, i.e., vomiting or diuretics use, and is typically treated with a chloride-rich solution such as normal saline (NS). Although NS is one of the most utilized Cl-rich solutions, high cation-gap amino acid (HCG-AA) predominantly comprises Cl and less sodium, making HCG-AA more efficient in correcting CDA. We herein report a case of CDA with chronic hyponatremia after frequent vomiting, which was successfully treated with HCG-AA without overcorrecting hyponatremia or causing hypervolemia. HCG-AA may be more beneficial than NS for treating hyponatremic or hypervolemic metabolic alkalosis.