Meat-diet-induced changes in gut microbiota are often accompanied with the development of various metabolic and inflammatory disorders. The exact biochemical mechanism underlying these effects is not well elucidated. This study aims to evaluate how meat proteins in high-fat diets affect tryptophan metabolism in rats. The high-chicken-protein (HFHCH) or high-pork-protein (HFHP) diets increased levels of skatole and indole in cecal and colonic contents, feces, and subcutaneous adipose tissue. The HFHCH and HFHP diets also increased the abundance of , the Family XIII AD3011 group, and in the cecum and colon, which may be involved in the production of skatole and indole. Additionally, high-meat-protein diets induced lower activity of skatole- and indole-metabolizing enzyme CYP2E1 in liver compared with low-meat-protein diets. This work highlights the negative impact of high meat proteins on physiological responses by inducing dysbiosis of gut microbiota and tryptophan metabolism.