This review article explores the synergistic effects of polyphenols and drugs in treating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota and signaling pathways. The authors highlight the importance of polyphenols in improving gut microbiota balance and their potential to synergize with drugs to enhance therapeutic outcomes. Key points include: 1. **Gut Microbiota and NAFLD**: The gut microbiota plays a crucial role in NAFLD development, with imbalances leading to increased inflammation and disease progression. Polyphenols can modulate gut microbiota, promoting beneficial bacteria and reducing harmful ones. 2. **Drugs and Gut Microbiota**: Various drugs used to treat NAFLD, such as statins, insulin sensitizers, and antioxidants, can affect gut microbiota. For example, statins can reduce pathogenic bacteria and increase beneficial bacteria, while insulin sensitizers can improve glucose metabolism and reduce inflammation. 3. **Polyphenols and Drugs**: The combination of polyphenols and drugs shows promising results in treating NAFLD. Polyphenols like flavonoids and phenolic acids can enhance the efficacy of drugs by improving gut microbiota and reducing side effects. For instance, the combination of polyphenols and statins can reduce cholesterol levels more effectively than statins alone. 4. **Mechanisms of Action**: The review outlines the mechanisms by which polyphenols and drugs work together to treat NAFLD. These include blocking the NF-κB pathway to reduce inflammation, activating PPAR receptors to increase fatty acid oxidation, and modulating signaling pathways such as AMPK, JAK/STAT, and PI3K/Akt. 5. **Future Directions**: The authors suggest that future research should focus on developing multi-omics technologies to identify patients who benefit from polyphenol-drug combinations and to optimize treatment plans for better therapeutic outcomes. Overall, the review emphasizes the potential of combining polyphenols and drugs to improve NAFLD treatment by targeting both gut microbiota and signaling pathways.This review article explores the synergistic effects of polyphenols and drugs in treating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota and signaling pathways. The authors highlight the importance of polyphenols in improving gut microbiota balance and their potential to synergize with drugs to enhance therapeutic outcomes. Key points include: 1. **Gut Microbiota and NAFLD**: The gut microbiota plays a crucial role in NAFLD development, with imbalances leading to increased inflammation and disease progression. Polyphenols can modulate gut microbiota, promoting beneficial bacteria and reducing harmful ones. 2. **Drugs and Gut Microbiota**: Various drugs used to treat NAFLD, such as statins, insulin sensitizers, and antioxidants, can affect gut microbiota. For example, statins can reduce pathogenic bacteria and increase beneficial bacteria, while insulin sensitizers can improve glucose metabolism and reduce inflammation. 3. **Polyphenols and Drugs**: The combination of polyphenols and drugs shows promising results in treating NAFLD. Polyphenols like flavonoids and phenolic acids can enhance the efficacy of drugs by improving gut microbiota and reducing side effects. For instance, the combination of polyphenols and statins can reduce cholesterol levels more effectively than statins alone. 4. **Mechanisms of Action**: The review outlines the mechanisms by which polyphenols and drugs work together to treat NAFLD. These include blocking the NF-κB pathway to reduce inflammation, activating PPAR receptors to increase fatty acid oxidation, and modulating signaling pathways such as AMPK, JAK/STAT, and PI3K/Akt. 5. **Future Directions**: The authors suggest that future research should focus on developing multi-omics technologies to identify patients who benefit from polyphenol-drug combinations and to optimize treatment plans for better therapeutic outcomes. Overall, the review emphasizes the potential of combining polyphenols and drugs to improve NAFLD treatment by targeting both gut microbiota and signaling pathways.