Objective: To investigate the effect of phytosterol nano-dispersion (PSND) with sodium caseinate-dextran glycosylation complex on lowing blood lipid and glucose in obese mice induced by high-fat diet. Methods: SPF C57BL/6J male mice were randomly divided into normal control group(CK group)， high-fat diet group(HFD group)， low (L)， middle (M) and high (H) dosing intervention groups. The mice of L， M and H groups separately drank the dispersions containing 0.3， 0.5 mg/mL and 0.7 mg/mL of phytosterol nano-dispersion. At the same time， they were fed with high-fat diet. After continuous feeding 15， 16 and 17 weeks， the fasting blood glucose， glucose tolerance test (GTT)， insulin tolerance test (ITT) were determined， respectively. After 18 weeks， body weight， subcutaneous fat， epididymal fat， brown fat， fat coefficient， liver index， serum biochemistry and other indicators were measured. The mRNA expression of HMG-CoA reductase (HMGCR)， low density lipoprotein receptor (LDL-R) and cholesterol 7α-hydroxylase (CYP7A1) in liver were assayed. Results: After 18 weeks of PSND intervention， compared with the HFD group， the gain of weight of mice in the low (L， 0.3 mg/mL)， middle (M， 0.5 mg/mL) and high (H， 0.7 mg/mL) groups decreased by 31.25％， 37.38% and 49.13%， respectively. The mass of subcutaneous fat decreased by 19.30%， 47.37% and 60.53% in three intervention groups， respectively. The mass of epididymal fat and brown fat decreased by 26.05% and 62.5% and in group H. At the same time， white fat cell enlargement and brown fat whiteness were inhibited with the intervention of phytosterol nano-dispersion. In H group， the liver index and contents of total cholesterol(TC)， low-density lipoprotein cholesterol (LDL-C)， glutamic oxalacetic transaminase (AST) and alanine transaminase(ALT) were significantly decreased. The expression of HMGCR (cholesterol synthesis related gene) was down-regulated in M and H groups， while the expression of LDL-R (cholesterol decomposition related gene) in all intervention groups and CYP7A1 in H group in were up-regulated. In M and H groups， the fasting blood glucose level of mice was reduced， and the glucose tolerance was improved as well as the insulin sensitivity in all intervention groups. Conclusion: phytosterol nano-dispersion with sodium caseinate-glucan glycosylation complex has significant effects of decreasing blood lipid and glucose and protecting the liver. This study provides the experimental basis for promoting the application of phytosterol in food.