The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.