Eluxadoline is a mixed opioid receptor agonist and antagonist approved for the treatment of diarrhea-predominant irritable bowel syndrome (IBS). It is believed to decrease visceral hypersensitivity without completely inhibiting intestinal motility. Pooled safety data from two phase three randomized trials have reported few cases of pancreatitis especially in patients with sphincter of Oddi (SO) dysfunction and cholecystectomy patients. We present a rare case of eluxadoline-induced recurrent pancreatitis in a 31-year-old female without a gallbladder. Her medical history was significant for irritable bowel syndrome with diarrhea (IBS-D), cholecystectomy, and depression. She was started on 75 mg of eluxadoline (the recommended dose for IBS-D patients without a gallbladder) three weeks prior to the first episode of pancreatitis. She had a recurrent episode of pancreatitis after few weeks and her symptoms and lipase levels improved significantly two days after stopping eluxadoline. The exact mechanism of eluxadoline to cause pancreatitis is unknown but it is believed to increase SO contractions. The absence of gallbladder prevents cholecystokinin mediated relaxation of the SO thus contributing more to spasms with eluxadoline. Few cases of severe pancreatitis and death have been reported even with the reduced dose of eluxadoline recommended for cholecystectomy patients. This case highlights the importance of considering drug-induced pancreatitis and avoidance of eluxadoline even in reduced doses in patients without a gallbladder.