The initial accounts of gallstone disease, a widespread ailment, were documented in the 15th century. However, historical records from preceding epochs remain scarce. This study aimed to examine the occurrence of gallbladder disease and cholelithiasis within ancient Mesopotamian cuneiform texts. As the primary resource for accessing Mesopotamian cuneiform documents and identifying relevant texts, Scurlock’s 2005 book was utilized. Six texts, believed to be connected to gallbladder disease, were selected. These texts underwent evaluation based on the presence of the terms ZÉ.GİG, ZÉ (denoting gallbladder disease), Pašittu (indicating cholelithiasis), and the five principal symptoms of gallbladder disease. The findings reveal an important relationship between Mesopotamian cuneiform texts and gallbladder disease, and date the historical timeline of gallstone disease and cholelithiasis back to the 1st millennium BC.