Celiac disease is a complex polygenic systemic disorder caused by dietary gluten exposure that selectively occurs in genetically susceptible people. The potential celiac disease is defined by the presence of celiac disease-specific antibodies and compatible human leukocyte antigen but without histological abnormalities in duodenal biopsies. At present, the only treatment is lifelong adherence to a gluten-free diet. Despite its effectiveness, the diet is difficult to maintain due to its cost, availability of gluten-free foods, and hidden gluten. The need to develop non-dietary treatment methods is widely recognized, but this is prevented by the absence of a pathophysiologically relevant preclinical model. Nonetheless, in vitro and in vivo models have made it possible to investigate the mechanisms of the disease and develop new treatment approaches: The use of foods with neutralized gluten, microbiota correction, cocktails of specific endoproteinase, polymer gluten binders, specific inhibitors of transglutaminases and inflammatory cytokines, and a vaccine based on allergen-specific therapy.