<p><b>Background:</b> The intestinal mucus layer constitutes an essential component of the gut barrier and plays a pivotal role in gastrointestinal health. Disruptions of this layer, particularly due to dietary fiber deficiency and mucus degrading bacteria, have been associated with various disorders including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), food intolerances, and other related conditions. While research on gastrointestinal microbiota has garnered significant attention, the knowledge of the mucus layer remains comparatively understudied.</p><p><b>Objective:</b> This review synthesizes current knowledge regarding the mucus layer and evaluates its clinical relevance for both the pathogenesis and therapeutic management of intestinal disorders, as well as their prevention.</p><p><b>Results:</b> An intact mucus layer provides critical protection against pathogenic factors while promoting microbiota homeostasis and functionality. Conversely, fiber deficiency accelerates mucus layer degradation, increases intestinal permeability, and promotes inflammatory processes. Therapeutic interventions such as dietary fibers, prebiotics, and postbiotics (e.g., short-chain fatty acids, SCFAs) demonstrate potential to restore mucus layer integrity and reinforce intestinal barrier function.</p><p><b>Conclusions:</b> The intestinal mucus layer represents an underappreciated yet crucial factor in intestinal health and disease pathogenesis. Fiber supplementation and postbiotic administration emerge as key therapeutic strategies for mucus layer reinforcement and regeneration. Further research is warranted to develop disease- and symptom-specific mucus-targeted therapies, including refined post- and prebiotic based therapeutic approaches.</p>