The nociceptin system, which consists of endogenous nociceptin/orphanin FQ and NOP receptors, is present in the central nervous system (CNS), as well as respiratory, cardiovascular, urogenital and gastrointestinal (GI) tissues. It is critically involved in nociception and pain signaling, as well as modulation of hormone and neurotransmitter release, stress responses and reversal of stress-induced analgesia. In the GI tract, the nociceptin system participates in the maintenance of homeostasis by affecting secretion and motility. Here we give an overview on the nociceptin system in the GI tract. The nociceptin system is an attractive target for novel drugs, which may be effective in the treatment of inflammatory or functional GI disorders, such as inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS).