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Research background: Global food security faces increasing threats from chemical contaminants, with N-nitrosodiethylamine (NDEA) emerging as a potent hepatotoxicant of significant concern. NDEA-induced hepatic injury causes a pathological triad: ( Experimental approach: The hepatoprotective and microbiota-modulating efficacy of extracellular polyphenols from Results and conclusions: After 28-day oral administration (50-100 (mg/kg)/day), LSP156 significantly improved somatic growth parameters (body mass gain) and organ indices in NDEA-induced mice. LSP156 increased the activities of SOD and catalase, as well as glutathione levels, and greatly reduced the liver function markers alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. It also improved liver cell damage in tissue samples compared to model controls. LSP156 halted the activation of STAT3 and reduced TLR4 levels, which lowered cyclooxygenase protein levels and protected the liver from damage. LSP156 enhanced the digestion and absorption of carbohydrates and proteins, as well as the biosynthesis of terpenoids such as ubiquinone in mice, by rectifying intestinal flora imbalances, modifying the flora structure and demonstrating a strong correlation between Novelty and scientific contribution: Fungal polyphenol LSP156 maintains balanced gut bacteria by simultaneously managing inflammation and oxidation. These findings suggest a new approach to designing drugs that target multiple factors in complex metabolic disorders.