ABSTRACT: Metabolic diseases, such as obesity, diabetes, and cardiovascular diseases, pose significant health challenges in contemporary society. The development of these diseases is closely related to the balance of gut microbiota, the functionality of metabolic products, and metabolic dysregulation across various tissues and organs. Tibetan tea, a traditional post-fermented tea originating from Ya'an, Sichuan in Southwest China, is known for its unique fermentation process and flavor, as well as its multitude of health benefits, such as acting as a prebiotic, antioxidant, blood sugar reducer, antithrombotic, and obesity prevention agent. This has sparked widespread interest among scholars both domestically and internationally in its potential to address metabolic diseases such as obesity, diabetes, hyperlipidemia, and thrombosis formation. However, current research has mostly focused on the effects on single tissues, with less exploration into the role of Tibetan tea in multi-tissue responses. Therefore, this study employed large-scale sequencing technologies to deeply analyze the impact of Tibetan tea extract intervention on the gut microbiota and peripheral blood, as well as on the metabolism of 10 different tissues and organs, including the brain, brown fat, heart, liver, kidneys, pancreas, colon, white fat, skeletal muscle, and bone marrow in C57BL/6J mice under both normal and high-fat diet conditions. The aim was to reveal the holistic response and mechanism of host metabolism to Tibetan tea intervention, thereby providing new insights into nutritional intervention strategies for metabolic diseases.