Acute interstitial nephritis (AIN) is known as a common cause of acute kidney injury, found in 15% to 27% of kidney biopsies. Drug-induced AIN is currently the most common cause of AIN. The most common medications causing AIN are antibiotics and nonsteroidal anti-inflammatory drugs. We describe a case of Citrullus colocynthis (herbal remedy for diabetes mellitus and weight reduction) that induced AIN. A 31-year-old woman with major thalassemia, diabetes mellitus, and hepatitis C infection was admitted because of flank pain and unexpected increase in serum creatinine level. She had been using Citrullus colocynthis for 3 months. Kidney biopsy results suggested AIN. She did not respond to steroid therapy and underwent hemodialysis. We suggest the use of Citrullus colocynthis as a herbal medicine with extreme caution.