Hyperlipidemia has high morbidity. We explored the novel activities of six Chinese herbs before and after fermentation for preventing hyperlipidemia. The herbs were fermented with white rot fungi Ganoderma lucidum, a strain of EN2. Lovastatin was used as the positive control. Mice were treated with those herbs before and after fermentation treatment for 15 d and then injected peritoneally with Triton 3393. After the treatment, the serum total cholesterol (TC) and triglyceride (TG) were measured. Moreover, the changes of the ingredients of those herbs were analyzed by fingerprint chromatography. The results showed that Herba leonuri before fermentation, Ramulus mori and Caulis lonicerae after fermentation, Radix sophorae flavescentis before and after fermentation showed activities to prevent hypertriglyceridemia, while Ramulus mori andHerba leonuri before fermentation showed activities to prevent hypercholesterolemia. In addition, some new ingredients were appeared after fermentation. In conclusion, the novel activities of these herbs to prevent hyperlipidemia were identified and the new ingredients that emerged after fermentation warrant further exploration.