Metabolic syndrome is a chronic metabolic disorder that has turned into a severe health problem worldwide. A previous study reported that large yellow tea exhibited better anti-diabetic and lipid-lowering effects than green tea. Nevertheless, the potential mechanisms are not yet understood. In this study, we examined the prevention effects and mechanisms of large yellow tea water extract (LWE) on metabolic syndrome using leptin receptor knockout () rats. Seven-week-old male and wild type (WT) littermate rats were divided into control group (KO) (n = 5), with LWE-treated group (KL) (n = 5), WT control group (WT) (n = 6), and WT with LWE intervention group (WL) (n = 6). Then, the rats were administered water or LWE (700 mg/kg BW) daily by oral gavage for 24 weeks, respectively. The results showed that the administration of LWE significantly reduced the serum concentrations of random blood glucose, total cholesterol, triglyceride, and free fatty acids, and increased glucose tolerance in rats. Moreover, LWE remarkably reduced hepatic lipid accumulation and alleviated fatty liver formation in rats. A mechanistic study showed that LWE obviously activated SIRT6 and decreased the expression of key lipogenesis-related molecules SREBP1, FAS, and DGAT1 in the livers of rats. Furthermore, LWE significantly improved microbiota dysbiosis via an increase in gut microbiota diversity and an abundance of the microbiota that produce short chain fatty acids (SCFAs), such as , , and . Finally, LWE supplementation increased the concentrations of SCFAs in the feces of rats. These results revealed that LWE attenuated metabolic syndrome of rats via the reduction of hepatic lipid synthesis through the SIRT6/SREBP1 pathway and the modulation of gut microbiota.