Monascus-fermented red mold dioscorea (RMD) has been proven to possess greater hypolipidemic effect than red mold rice (RMR) even though they include equal levels of cholesterol-lowering agent monacolin K. However, higher concentrations of yellow pigments (monascin and ankaflavin) were found in RMD than in RMR. In this study, purified monascin and ankaflavin were administered to hyperlipidemic hamsters for 8 weeks, respectively, to test whether these two compounds were novel hypolipidemic ingredients. In the statistical results, monascin and ankaflavin showed significant effect on lowering cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in serum, as well as aorta lipid plaque (p < 0.05). Importantly, monascin and ankaflavin, unlike monacolin K, were able to perform up-regulation rather than down-regulation on high-density lipoprotein cholesterol (HDL-C) levels in serum. This finding not only explained why RMD showed greater hypolipidemic and HDL-C-raising effect than RMR but also proved that monascin and ankaflavin would act as novel and potent hypolipidemic ingredients.