Prebiotics can promote the growth of probiotics, cocombine of these is called synbiotics, and synbiotics is powerful regulators of gut microbiota. Intestinal microbiota plays an important role in nonalcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. This study aims to investigate the effect of synbiotics combination of probiotics (Streptococcus Bifidobacterium and Streptococcus thermophilus) and prebiotics (Inulin) in vivo model of early NAFLD using yogurt as carrier. The results demonstrate that the yogurt with synbiotics combination group (HS) improves the biochemical indicators related to total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and insulin resistance (IR) in mice (P< .01). HS improves the development of lipid metabolism and inflammation by activating the AMPK and NFκB signaling pathway. In addition, HS restores the intestinal barrier dysfunction and inflammation caused by a high-fat diet. The 16S rRNA demonstrates that the gut microbiota composition of mice treated with HS is significantly altered specifically, the Firmicutes/Bacteroidetes ratio is significantly lower than in HFD-fed mice (P< .01). Our findings suggest the applicability of HS in preventing obesity-related NAFLD via its antioxidant, anti-inflammatory, and improved lipid metabolism by the gut-liver axis and provide a solid theoretical foundation for developing prebiotics for the prevention of NAFLD.