This study investigated the inhibitory effects of super-comminuted dietary fiber from pomelo peel (SCPPDF) against high-fat diet (HFD)-induced obesity in mice. Mice were divided into five groups, which were fed with a normal diet, HFD, and HFD supplemented with low, medium, and high doses of SCPPDF for six weeks, respectively. Results showed that the SCPPDF supplementation effectively decreased the body weight and fat accumulation in liver and epididymal tissues in the HFD-fed mice, and decreased serum levels of triglycerides, low-density lipoprotein cholesterol, and total cholesterol. In addition, SCPPDF supplementation also decreased the Firmicutes to Bacteroidetes ratio (F/B), increased the relative abundances of short-chain fatty acids-producing bacteria, such as Lactobacillus, Bifidobacterium, and Allobaculum, reduced those of pathogenic bacteria, such as Staphylococcus and Corynebacterium_1, thereby regulating the HFD-induced imbalance of gut microbiota in mice. These findings indicated that SCPPDF could effectively inhibit obesity by regulating blood lipid levels, improving gut microbiota. SCPPDF has great potential to be developed into prebiotics or functional foods.