During nutrient deprivation, autophagy provides the constituents required to maintain the metabolism essential for survival. Recently, genome-wide association studies have identified genetic determinants for susceptibility to Crohn's disease (CD) such as ATG16L1 and IRGM that are involved in the autophagy pathway. Both disease-carrying NOD2 mutations and ATG16L1 mutations may result in impairment of autophagy. Impairment in autophagy results in impaired clearance of microbes. Ileal CD is associated with Paneth cell loss of function such as decreased production of α-defensins, which may arise from mutations in NOD2 or autophagy genes. Nutrients are able to modify several cellular pathways and in particular autophagy. We summarize the contribution of a variety of dietary components to activate autophagy. Understanding the crosstalk between nutrients and autophagy in the intestine may provide novel targets that have therapeutics potential in intestinal inflammation. Nutrient activation of autophagy may contribute to restoring the Paneth cell loss of function in ileal CD.