•Intestinal barrier dysfunction is often seen in patients with FGIDs.•More, and activated, intestinal mucosal mast cells have been observed in FGIDs.•Mast cells are known regulators of barrier function.•Stabilizing/blocking mast cells provide a novel approach for treatment of FGIDs.•Probiotics have shown promising effects on the mucosal barrier in FGIDs. The intestinal mucosa is constantly exposed to harmful luminal content, and uptake is closely controlled and regulated by neuro-immune factors. If control is broken, it might lead to ongoing enhanced mucosal permeability, potentially resulting in functional gastrointestinal disorders. The importance of mast cells in the regulation of the mucosal barrier has become obvious, and increased numbers and more activated mast cells have been observed in irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease. To target the disturbed mucosal permeability, directly or via mast cells, is therefore currently of major interest. For example, administration of mast cell stabilizers and probiotics have shown promising effects in patients with functional gastrointestinal disorders.