Globally, the incidence of diseases such as obesity, fatty liver and hyperlipidaemia has increased drastically in recent years. This study investigated the direct treatment of obesity and its associated metabolic disorders using peanut-natto in a high-fat diet (HFD)–induced mouse model of obesity. After 6 weeks of treatment, peanut-natto significantly reduced the body and abdominal fat weight of mice with obesity, decreased the fat cell area and fat droplet accumulation in the liver and improved the colon structure by regulating the levels of intestinal lipid metabolism-related proteins such as CD36 and FATP4. Compared with the untreated HFD group, peanut-natto significantly reduced the serum levels of LDL-C, TG and T-CHO. Metagenomic analysis revealed that natto can restore the abundance of gut microbiota to a certain extent and increase the Bacteroidetes-to-Firmicutes ratio. Non-targeted metabolomics analysis indicated a metabolism disorder that was obviously improved by peanut-natto treatment via the regulation of α-linolenic acid metabolism, linoleic acid metabolism, unsaturated fatty acid biosynthesis and lipid decomposition in fat cells. These results provide a scientific basis for using peanut-natto as a new food product to prevent obesity, improve metabolic disorders and balance the intestinal microbiota.