The enteric nervous system (ENS) is a highly conserved, yet complicated network of neurons and glial cells located throughout the gut wall that controls digestive processes and gastrointestinal (GI) homeostasis. The intestinal epithelium, the immune system, and the gut microbiota are just a few examples of the cellular networks that the ENS interacts with on a variety of levels to maintain GI function. The presence or absence of nutrients in the intestinal lumen may cause short- and/or long-term changes in neurotransmitter expression, excitability, and neuronal survival, which ultimately affect gut motility, secretion, and permeability. Hence, the ENS should be identified as a key factor in initiating coordinated responses to nutrients. In this review we summarize current knowledge on nutrient-dependent ENS activity and how ENS secondary to nutrition may affect likelihood of developing inflammatory bowel disease. Our findings highlight that nutrients interact with enteroendocrine cells in the gut, triggering hormone secretion that plays a crucial role in signaling food-related information to the brain and regulating metabolic processes such as feeding behavior, insulin secretion, and energy balance; however, the complex interactions between nutrients, the ENS, and the immune system require further research to understand their contributions to GI disorders and potential therapeutic applications in treating obesity and metabolic diseases. Lay Summary: The enteric nervous system (ENS) controls digestion and interacts with nutrients in the gut to regulate processes like gut movement and hormone release, affecting metabolism and overall gut health. This review highlights the need for further research on how nutrient-ENS interactions contribute to conditions like inflammatory bowel disease, obesity, and metabolic disorders.