Gut-brain dysregulation has been recognized by the scientific community as being crucial to the understanding of chronic gastrointestinal conditions, and this has translated into the practice of a newly established discipline, psychogastroenterology. Along with psychotherapy, antidepressants (a subtype of central neuromodulators) have been proposed as treatments for gut-brain disorders that might benefit both psychological and gastrointestinal health. Antidepressants have been found to be effective for the treatment of comorbid anxiety and depression, pain and impaired sleep. Although the efficacy of antidepressants is well established in disorders of gut-brain interaction (DGBI), evidence is only now emerging in IBD. This Perspective discusses the use of antidepressants in DGBI and IBD, focusing on how what we have learnt about the role of antidepressants in DGBI could be applied to help optimize the management of IBD.