The oral administration of synthetic drugs can effectively reduce blood lipid levels, but adverse reactions may occur. Because of this, the hypolipidemic ability of natural products has been increasingly investigated. We evaluate the safety and hypolipidemic characteristics of a water-soluble blue pigment extracted using HPD-400 resin from the fungus Quambalaria cyanescens. Hypolipidemic ability was examined by constructing a hyperlipidemia model with different doses of blue pigment (50, 100, and 200 mg/kg. mouse body weight) for 28 d. Blue pigment purity increased from 20.32% to 70.70% following treatment with HPD-400 resin. Acute toxicity tests revealed blue pigment sourced from Q. cyanescens to have no toxic effects on mouse body weight, mortality, or behavioral characteristics. Subacute toxicity tests revealed no significant differences in food intake, body weight, or organ weights between treatment groups and controls. Histopathological examination of the liver and kidney tissues of mice administered blue pigment were normal, and serum enzyme activities and blood constituents were also within normal ranges. Blue pigment can significantly reduce the weight of mice, reduce liver and kidney damage and fat accumulation. It can also reduce total cholesterol, triglyceride and low density lipoprotein cholesterol in serum and liver tissue, and increase the level of high density lipoprotein cholesterol. Reduce the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, urea and uric acid in serum. Increase the activities of total superoxide dismutase, glutathione peroxidase and catalase in serum and liver tissue, reduce the content of malondialdehyde, and up-regulate liver lipase and lipoprotein lipase. Our work proves that blue pigment is nontoxic, has the function of reducing blood lipid, and can alleviate obesity-related symptoms by regulating lipid metabolism and oxidative stress.