This study presents a novel approach for alcohol detoxification using a biomimetic-nanozyme amyloid hydrogel. The hydrogel is composed of single-site iron-anchored amyloid fibrils derived from β-lactoglobulin, a milk protein with abundant nitrogen atoms that can coordinate with iron. The hydrogel mimics the coordination structure of horseradish peroxidase and efficiently catalyzes the oxidation of alcohol into acetic acid, avoiding the formation of the more toxic acetaldehyde. When administered orally to mice, the hydrogel significantly reduces blood alcohol levels by 55.8% within 300 minutes after alcohol intake, without causing additional acetaldehyde accumulation. It also provides protection to the liver and mitigates intestinal damage and dysbiosis associated with chronic alcohol consumption, offering a promising strategy for effective alcohol detoxification. The hydrogel is synthesized by impregnating β-lactoglobulin fibrils with iron ions, resulting in a stable, highly dispersed iron-based nanozyme. The structure of the hydrogel was characterized using various techniques, including transmission electron microscopy (TEM), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray absorption spectroscopy (XAS). These analyses confirmed the presence of single-site iron atoms coordinated with nitrogen atoms in the β-lactoglobulin fibrils. The hydrogel exhibits peroxidase-like activity, efficiently catalyzing the oxidation of various substrates, including TMB, ethanol, and acetaldehyde. The catalytic efficiency of the hydrogel was evaluated using steady-state kinetic assays, revealing high turnover numbers and catalytic efficiencies. The hydrogel also demonstrated excellent stability, retaining over 95% of its activity after 3 hours of digestion in simulated gastric and intestinal fluids. In vivo studies showed that the hydrogel significantly reduced blood alcohol levels in mice intoxicated with alcohol, with no accumulation of acetaldehyde. The hydrogel also protected the liver and reduced intestinal damage and dysbiosis, indicating its potential as a therapeutic approach for alcohol-related conditions. The study highlights the potential of biomimetic-nanozyme hydrogels as a promising solution for alcohol detoxification, offering a safe and effective alternative to traditional methods.This study presents a novel approach for alcohol detoxification using a biomimetic-nanozyme amyloid hydrogel. The hydrogel is composed of single-site iron-anchored amyloid fibrils derived from β-lactoglobulin, a milk protein with abundant nitrogen atoms that can coordinate with iron. The hydrogel mimics the coordination structure of horseradish peroxidase and efficiently catalyzes the oxidation of alcohol into acetic acid, avoiding the formation of the more toxic acetaldehyde. When administered orally to mice, the hydrogel significantly reduces blood alcohol levels by 55.8% within 300 minutes after alcohol intake, without causing additional acetaldehyde accumulation. It also provides protection to the liver and mitigates intestinal damage and dysbiosis associated with chronic alcohol consumption, offering a promising strategy for effective alcohol detoxification. The hydrogel is synthesized by impregnating β-lactoglobulin fibrils with iron ions, resulting in a stable, highly dispersed iron-based nanozyme. The structure of the hydrogel was characterized using various techniques, including transmission electron microscopy (TEM), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray absorption spectroscopy (XAS). These analyses confirmed the presence of single-site iron atoms coordinated with nitrogen atoms in the β-lactoglobulin fibrils. The hydrogel exhibits peroxidase-like activity, efficiently catalyzing the oxidation of various substrates, including TMB, ethanol, and acetaldehyde. The catalytic efficiency of the hydrogel was evaluated using steady-state kinetic assays, revealing high turnover numbers and catalytic efficiencies. The hydrogel also demonstrated excellent stability, retaining over 95% of its activity after 3 hours of digestion in simulated gastric and intestinal fluids. In vivo studies showed that the hydrogel significantly reduced blood alcohol levels in mice intoxicated with alcohol, with no accumulation of acetaldehyde. The hydrogel also protected the liver and reduced intestinal damage and dysbiosis, indicating its potential as a therapeutic approach for alcohol-related conditions. The study highlights the potential of biomimetic-nanozyme hydrogels as a promising solution for alcohol detoxification, offering a safe and effective alternative to traditional methods.