Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered defecation, usually accompanied by abdominal bloating or distension. The integrated model of bidirectional interaction between the central, autonomic, enteric nervous system, the microbiome, and the gut barrier allows a better understanding of the pathophysiology of IBS, as well as consideration of potential therapeutic strategies. IBS with predominant diarrhea (IBS-D) represents a therapeutic challenge. Dietary changes or restrictions are most commonly used by patients in an attempt at symptom control. Therefore, a number of diets, especially low-FODMAP diet, have increasingly gained interest as a therapy for IBS-D or mixed IBS. However, this kind of diet, while effective, is not exempt of problems. It is therefore necessary that other therapeutic options be considered while bearing pathophysiological mechanisms and general symptom management in mind.