Celiac disease (CD), a chronic inflammatory disorder, is triggered by the ingestion of gluten peptide. Wheat gluten contains gliadins and glutenins fractions, where gliadin peptides are the main cause of CD and nonceliac gluten sensitivity development. Keeping a strictgluten-free diet is the only effective treatment for CD. In recent years, lactic acid bacterial and fungal prolyl endopeptidases (PEP) have been proposed as the sources of proteolytic enzymes for the complete elimination of gluten peptides, and have also proved as a potential common therapeutic agent for CD treatment. Considering these indications, a special focus was devoted to AN-PEP-secreted PEP. Herein, we review the proteolytic enzymes produced by microorganisms, especially by the fungal strain, Aspergillus niger (AN), and discuss its beneficial properties against toxic effects of α-gliadin digestion in affected patients. The present review reveals the importance of proteolytic proteases in industrial applications; from an economic perspective, AN-PEP protease is an appropriate choice for making high-quality gluten-free products. Manuscript profile