Present in the digestive system, sphingolipids are responsible for multiple important physiological and pathological processes. On the membrane of intestinal epithelial cells sphingolipids contribute to structural integrity, regulate absorption of nutrients and may act as receptors for some microorganisms and their toxins. Moreover, bioactive lipid messengers such as ceramide and sphingosine-1-phosphate influence cellular growth, differentiation and programmed cell death, apoptosis. Further studies are needed to fully explore the clinical implications of sphingolipids in neoplastic and inflammatory diseases in the gastrointestinal tract. Pharmacological compounds which regulate metabolism of sphingolipids can be potentially useful in treatment of colon cancer, inflammatory bowel diseases or nonalcoholic fatty liver disease. The aim of this work is to present a critical review of the physiological and pathological role of sphingolipids in the digestive system.