Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition, frequently comorbid with heterogeneous gastrointestinal (GI) pathologies, including Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), and functional motility disorders. Emerging evidence implicates the microbiota-gut-brain axis in the pathogenesis of these GI anomalies. Dietary polyphenols, characterized by potent antioxidant, anti-inflammatory, and neuromodulatory properties, represent a promising candidate approach for exploring the management of these comorbid conditions. This review critically examines the proposed molecular mechanisms by which specific phenolic compounds (e.g., resveratrol, quercetin and curcumin) may mitigate GI symptoms in ASD. Mechanistically, preclinical evidence suggests that polyphenols may help restore intestinal barrier integrity by upregulating tight junction proteins, suppress mucosal inflammation via the downregulation of Nuclear Factor Kappa B (NF-κB)/NOD-like Receptor Family Pyrin Domain Containing 3(NLRP3) pathways, and regulate gut motility through enteric neurotransmitter modulation. However, direct clinical efficacy in individuals with ASD remains largely unproven. Future clinical directions are proposed, focusing on the incorporation of low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) natural food matrices and the development of controlled food fortification strategies over isolated high-dose supplementation. This work provides a theoretical foundation and a concise roadmap for advancing polyphenol-based dietary interventions in the management of GI pathophysiology in ASD.
