Pathogenetically characterized by the absence of celiac disease and wheat allergy, non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the consumption of gluten-containing foods that relieved by a gluten-free diet. Since it is very difficult to maintain a complete gluten-free diet, there is a high interest in discovering alternative strategies aimed at reducing gluten concentration or mitigating its toxic effects. Plant-based dietary models are usually rich in bioactive compounds, such as polyphenols, recognized to prevent, delay, or even reverse chronic diseases, including intestinal disorders. However, research on the role of polyphenols in mitigating the toxicity of gluten-containing foods is currently limited. We address the metabolic fate of dietary polyphenols, both as free and bound macromolecule-linked forms, with particular reference to the gastrointestinal compartment, where the concentration of polyphenols can reach high levels. We analyze the potential targets of polyphenols including the gluten peptide bioavailability, the dysfunction of the intestinal epithelial barrier, intestinal immune response, oxidative stress and inflammation, and dysbiosis. Overall, this review provides an updated overview of the effects of polyphenols as possible dietary strategies to counteract the toxic effects of gluten, potentially resulting in the improved quality of life of patients with gluten-related disorders.