<p>Hepatic encephalopathy is one of the most severe complications of liver cirrhosis, with a high mortality rate following its onset. Treatment for hepatic encephalopathy is challenging, recurrence rates are high, and the condition exhibits significant individual variability. Current treatments lack personalization, leading to substantial waste in healthcare costs. Extensive research indicates that specific gut macrobiotic dysbiosis precedes the onset of hepatic encephalopathy. Modulating gut macrobiotic can prevent and treat hepatic encephalopathy by protecting intestinal and blood-brain barrier function, reducing neurotoxin production, enhancing hepatic detoxification capacity, and safeguarding normal neurotransmitter function. This review discusses strategies for treating hepatic encephalopathy through gut macrobiotic intervention from the perspective of Predictive, Preventive, and Personalized Medicine (PPPM/3PM). The conclusion is that gut microbiota can serve both as personalized indicators to predict the risk of hepatic encephalopathy and as personalized therapeutics to prevent and treat the condition. Notably, lifestyle modifications, as the most cost-effective intervention, play a crucial role in both preventing hepatic encephalopathy and modulating gut microbiota.</p> Graphical abstract <p></p>