The growing prevalence of obesity is being increasingly acknowledged as a major public health issue. This mainly stems from the excessive intake of dietary fats. (DO), recognized as an herb with dual roles of food and medicine, is renowned for its diverse health-promoting effects. Nevertheless, the specifics of its antiobesity and anti-inflammatory properties and the underlying mechanisms are still obscure. The present study shows that treatment with extract (DOE) alleviates obesity, liver steatosis, inflammation, and oxidative stress in rats that are obese due to a high-fat diet (HFD). Firstly, with respect to HFD obese rats, higher doses of DOE significantly reduced TG, TC, LDL-C, blood glucose, and liver AST and ALT, along with lipid droplets. Meanwhile, DOE supplementation significantly reduced oxidative stress induced by ROS and MDA and increased the levels of GSH-Px and SOD in liver tissues. Furthermore, integrated analysis of transcriptomic and microbiomic data revealed that DOE modulated inflammatory responses through the NF-κB/IκB pathway. This regulatory mechanism was evidenced by corresponding changes in the protein expression levels of both NF-κB and IκB. Additionally, DOE was found to modulate gut microbiota composition in obese rats, specifically reducing the relative abundance of while increasing beneficial bacterial populations, particularly the genera and . These findings suggest that DOE may help retain the homeostasis of the gut microbiota and improve metabolic health by regulating inflammation in the liver and intestine, thereby providing protection against obesity and related metabolic syndromes. Our study demonstrates that DOE, as a natural botanical extract, can effectively facilitate the prevention or treatment of metabolic syndrome through precision dietary interventions.