Carnosic acid (CA) is a bioactive phenolic diterperne compound found in sage and rosemary. The present study investigated the beneficial effects of CA (50 and 100 mg per kg bw) in diet-induced obese mice and the underlying mechanisms of action. After the intervention, the physiology, lipid metabolism, and tissue morphology, as well as the inflammation, gut microbiota, and metabolomics in the colon were measured. We found that CA improved the composition and metabolism of the gut microbiota in obese mice, with Akkermansia being the dominant bacterium negatively correlated with obesity and various fecal metabolites. Regarding the intestinal barrier function, CA promoted the expression of tight junction proteins and inhibited the TLR4/MyD88/NF-κB signaling pathway in obese mice to alleviate colonic inflammation. These results suggest that CA improved multiple aspects of gut health in diet-induced obesity in mice, providing a scientific basis for future clinical studies in humans.