Acrylamide is a well-known potent carcinogen and neurotoxin that, until now, has not been sufficiently investigated with regard to its effects on lipid metabolism. We investigated physiological effects of acrylamide (AA) on lipoprotein metabolism using human macrophages, dermal cells, and zebrafish models. Functional and structural properties of lipoproteins were modified by AA (final concentration of 5–100 mM) with loss of antioxidant ability and multimerization of apoA-I in vitro. AA exacerbated LDL oxidation, degradation, and LDL uptake into macrophages with increased ROS production. In human cells, treatment of AA (1–100 μM) caused cellular senescence of dermal cells with severe cytotoxicity. Waterborne exposure of zebrafish in cage water containing AA (300 ppm) resulted in acute death within 26 h along with elevation of body weight, blood glucose, triglyceride, and hepatic inflammation. AA exposure caused fat accumulation in liver in a dose-dependent manner. In conclusion, AA affected lipoprotein metabolism to result exacerbation of atherosclerosis. Exposure of zebrafish to AA resulted in acute inflammatory death with hyperlipidemia.