Opiod drugs are widely used to treat chronic pain, but their misuse can lead to tolerance, dependence, and addiction and have created a significant public health problem. In addition, food-derived opioid peptides, known as exorphins, like gluten exorphins have been shown to have harmful effects in certain pathologies like celiac disease, for example. Several studies support the involvement of the opioid system in the development of disorders such as autism spectrum syndrome. Moreover, bidirectional communication between the intestine and brain has been shown to be altered in various neurodegenerative diseases including Alzheimer´s and Parkinson´s. The presence of opiod receptors in both the digestive tract and the central nervous system (CNS) suggests that opioid drugs and exorphins may modulate the gut-brain axis. Morphine, for example, has shown a dysbiotic effect on the bacterial microbiota in addition to inducing an increase in intestinal permeability facilitating bacterial translocation. Furthermore, certain components of bacteria can modify the expression of opioid receptors at the central level increasing sensitivity to pain. Strategies based on use of probiotics have resulted in improvements in symptoms of autism and Parkinson´s disease. In this manuscript, we review the role of the opioid system in disorders and CNS pathologies and the involvement of the gut-brain axis.Copyright © 2020 Elsevier Ltd. All rights reserved.