This study aimed to investigate the weight-reducing effect of scutellarin (SCU) in obese mice and elucidate its potential mechanisms from the perspective of gut microecology. An obesity model was established in C57BL/6J mice using a high-fat diet. The mice were divided into normal control, model, and SCU intervention groups. The SCU-treated group received SCU by intragastric administration at 400 mg/(kg·d) for ten weeks alongside high-fat diet feeding, while control and model groups were given equal volumes of PBS. Body weight changes were monitored; adipose coefficient and liver coefficient were measured; serum levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) were detected by ELISA; pathological changes in colon tissue were observed by HE staining; and composition/functional alterations of gut microbiota were analyzed via 16S rDNA V4 region sequencing. Results showed that compared with the model group, SCU-treated mice exhibited significant reductions in body weight, adipose coefficient, and liver coefficient. Serum levels of IL-6, IL-10, and TNF-α were significantly decreased. Structural disorder of colonic villi was alleviated, while richness and diversity of gut microbiota increased. At the phylum level, the proportion of Firmicutes significantly increased, whereas Bacteroidetes and Proteobacteria significantly decreased. Genus-level analysis revealed increased relative abundances of Prevotella and Pseudoflavonifractor but decreased abundances of Sutterella, Blautia, and Eubacterium. Gut microbiota showed enhanced functional expression in DNA damage repair pathways and improved amino acid metabolic disorders. SCU may exert anti-obesity effects by modulating gut microbiota structure/function, enhancing intestinal barrier integrity, and suppressing systemic inflammation, providing experimental evidence for its application in metabolic disease intervention.