The gastrointestinal tract represents the largest mucosal membrane surface and is the one of the most complex human organs. The intestinal barrier dysfunction contributes to systemic immune activation. The mucosal immune system has extremely arduous tasks to resist invaders and promote tolerance of food antigens and the microbiota. The intestinal mucosal immune system fulfills these tasks through complex interactions between immune cells and the local microenvironment in intestine. Intestinal Epithelial Cells (IECs) play important roles in these complex interactions. IECs not only constitute the first barrier of the intestine but also are crucial for integrating external and internal signals and for coordinating the ensuing immune response. Dendritic Cells (DCs) play key roles in shaping the intestinal immune response by their ability to coordinate protective immunity and immune tolerance in the host. DCs are pivotal actors in the connection between innate and adaptive immune responses. The IECs coordinate with the DCs in immune recognition, tolerance and host defense mechanisms. In this review, we will summarize how IECs orchestrate intestinal DCs in intestinal homeostasis and diseases.