The effects of indole-3-propionic acid (IPA) on gut microbiota composition and metabolic parameters in highfat diet-induced obese mice were investigated. Male C57BL/6J mice were randomly divided into three groups: low-fat diet (LFD), highfat diet (HFD), and IPA intervention (HFD+IPA) groups. After 16 weeks of intragastric administration, body weight, liver weight, and peritesticular adipose tissue weight were measured, and lipid deposition was assessed. Serum triglyceride (TG) and total cholesterol (TC) levels were determined using ELISA. Gut microbiota composition and abundance were analyzed using 16S rRNA gene sequencing. The results showed that, compared with the HFD group, IPA intervention significantly reduced body weight gain (P<0.05). Liver weight, peritesticular adipose tissue weight, and liver index decreased by 26.30%, 29.00%, and 26.98%, respectively. Serum TG and TC levels decreased by 23.11% and 19.53%, respectively. Moreover, the relative abundance of Akkermansia in the gut microbiota increased by approximately 2-fold following IPA treatment. These findings suggest that IPA may alleviate metabolic abnormalities in obese mice by modulating the gut microbiota, particularly by increasing beneficial bacteria such as Akkermansia. A theoretical basis and potential application value for targeting gut microbiota with tryptophan metabolites in obesity intervention is provided.