Abstract Context A gluten-free diet (GFD) is the recommended treatment for gluten-dependent disease. In addition, gluten withdrawal is popular and occasionally is suggested as a treatment for other autoimmune diseases (ADs). Objective The current systematic review summarizes those entities and discusses the logic behind using a GFD in classical non–gluten-dependentADs. Data Sources A search for medical articles in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo published between 1960 and 2020 was conducted, using the key words for various ADs and GFDs. Data Exxtraction Eight-three articles were included in the systematic review (using PRISMA guidelines). Data Analysis Reduction in symptoms of ADs after observance of a GFD was observed in 911 out of 1408 patients (64.7%) and in 66 out of the 83 selected studies (79.5%). The age of the patients ranged from 9 months to 69 years. The duration of the GFD varied from 1 month to 9 years. A GFD can suppress several harmful intraluminal intestinal events. Potential mechanisms and pathways for the action of GFD in the gut – remote organs’ axis have been suggested. Conclusion A GFD might represent a novel nutritional therapeutic strategy for classical non–gluten-dependent autoimmune conditions.