Gastrointestinal tract diseases are recognised as autoimmune based on typical histopathology, presence of autoantibodies in serum and clinical response to immunosuppressive therapy. Like in other autoimmune diseases, the inducing factor is unknown; however, accumulating data suggests an increasing role of microbiota homeostasis and relation between the immune system (mucous-associated lymphoid tissue) and microbiota in intestinal lumen. The inflammation process is now described as autoinflammation with inflammasome formation or autoimmune chronic inflammation with overproduction of pro-inflammatory cytokines. Diagnostic procedures include autoantibodies assay, histology of biopsy from intestinal mucous, genetic background (especially in celiac disease) and clinical symptoms. Therapy is adjusted to pathomechanism including regulation of microbiota homeostasis with pre-biotics and probiotics, inhibition of inflammatory process with steroids, classical immunosuppression and anti-cytokine monoclonal antibodies and haematopoietic stem cells transplantation in severe cases with therapy resistance, progression and life-threatening course. The aim of this chapter is to review mechanisms of autoinflammation and autoimmunity, diagnosis and therapy of gastrointestinal tract.