This study investigated the hepatotoxic effects and mechanisms of high-dose tea polyphenols on zebrafish liver based on the gut-liver axis theory. An 8-week rearing experiment evaluated various aspects such as physiological and biochemical indicators, histology, gut microbiota, and liver transcriptomics of zebrafish. The results showed that feeding zebrafish a diet rich in high-dose tea polyphenols disrupted their hepatic lipid metabolism, ultimately causing liver damage. Tea polyphenols regulated signaling pathways related to “lipid metabolism and absorption” and “fatty acid degradation”, promoting the uptake of fatty acids and cholesterol by liver cells, inhibiting fatty acid oxidation and excretion, and causing liver fat accumulation. Additionally, high-dose tea polyphenols altered the composition of the gut microbiota, reducing microbial diversity and decreasing the production of intestinal short-chain fatty acids (SCFAs). As a result of the gut-liver axis interaction, low levels of SCFAs and harmful bacteria from the intestine were able to enter the liver through the portal vein, activating hepatic pro-inflammatory factors and causing liver inflammation. The accumulation of liver fat further promoted the expression of pro-inflammatory factors and transported them to the intestine through the bile duct, exacerbating intestinal damage in zebrafish. Therefore, caution should be exercised when using tea polyphenols as a nutritional supplement or medication, especially at high doses and with long-term use, to be aware of their potential adverse effects.