Siraitia grosvenorii (SG), a traditional edible medicine in China, has shown potential application in health foods due to multiple bioactivities. However, few comparative studies have investigated the effect of daily intake of SG products by traditional drinking way on alleviating metabolic disorders caused by long-term high fat and high sugar diet (HF-HSD). This study investigated the effects of 2 commercial SG products (SG juice containing comprehensive compositions and mogrosides extract containing high content of mogroside V) supplement on fat content, lipid accumulation, colon barrier and gut microbiota in a 38-week HF-HSD mice trial. Results showed that the SG intervention could decrease the weight gain and body fat content, alleviated lipid accumulation, low-grade inflammation and colon barrier injury. SG juice intake was found to increase the antioxidant enzyme activities of serum glutathione peroxidase and liver superoxide dismutase. 16S rRNA analysis found that SG could restore the gut microbiota with downregulation of harmful bacteria increased by HF-HSD and enhancement of the abundances of beneficial genus. In particular, SG juice significantly enriched taxonomic family Prevotellaceae and genus Alloprevotella. These results indicated that SG might be a functional additive to prevent disease risk caused by excess fat and sugar diet, and active ingredients resulting to the discrepancy of performance especially on gut microbiota are worthy of in-depth investigation.