OBJECTIVE: This study investigated the mechanisms related to lipid metabolism regulation after combined supplementation with deer antler polysaccharides and postbiotics. METHODS: Thirty-two male mice were divided into high-fat diet, HD + deer antler polysaccharides, HD + RESULTS: Supplementation with deer antler polysaccharides and postbiotics significantly inhibited weight gain in obese mice, reduced serum total cholesterol, triglyceride, and low-density lipoprotein levels and markedly increased the serum high-density lipoprotein level. Additionally, hepatic lipid droplet accumulation and adipocyte hypertrophy improved. The expressions of the lipid synthesis genes, sterol regulatory element-binding protein 1 (i.e. CONCLUSION: Thus, combined deer antler polysaccharides and postbiotic supplementation regulated obesity in mice, potentially by modulating lipid synthesis and inflammation-related gene expression.