Polysaccharides from edible and medicinal mushrooms help protect the stomach and intestinal lining by strengthening the mucus barrier, reducing oxidative stress, calming inflammation, and supporting healthy gut bacteria. This review shows that a polysaccharide’s structure matters: factors like molecular weight, sugar makeup, and branching shape how well these compounds boost protective proteins such as MUC2, tighten junctions like ZO-1 and occludin, and aid healing after damage from stress, diet, infections, or medications.