We investigated the blood lipid regulation effects and mechanism of a functional Natto yogurt in a high-fat diet-induced hyperlipidemia mouse model. Natto yogurt was characteristically fermented by Bacillus natto and Lactobacillus plantarum with milk-soy dual protein as substrates. After 5 weeks of Natto yogurt consumption, the body weight, fat, and liver weight of mice were significantly improved, while serum levels of TG, TC, LDL, ALT, TBIL, and TBA were reduced. Natto yogurt significantly decreased the area of liver fat infiltration and the number of lipid droplets. In mechanism, we found that Natto yogurt can inhibit fatty acid synthesis and enhance fatty acid catabolism by regulating the expression of PPARα, PPARγ, CD36 and FAS in the liver. Moreover, Natto yogurt increased the ratio of Bacteroidetes to Firmicutes in the intestine. These results provide a possibility for Natto yogurt as a dual protein functional food to prevent and treat hyperlipidemia and obesity.