In this study, a large Clitocybe maxima mycelium biomass was obtained by submerged cultivation under optimal conditions. Three test samples from lyophilized mycelia, including hot water extract (CW) and elutes from solvents with different polarity (CA and CB), were combined and used to explore antioxidant and antihyper-lipidemic activities in vitro and in vivo. The CA group showed the highest DPPH free radical scavenging activity and iron-reducing capability at concentrations of 6.0% and 3.0% (w/v), respectively. Further, the CA group showed the highest glutathione peroxidase and superoxide dismutase activities at a dose of 0.25 mg/kg body weight (CA-0.25 group) in all hyperlipidemic hamsters tested. Serum lipid levels (apart from high-density lipoprotein cholesterol levels) of hamsters in the CA-0.25 group were lower than those of hamsters in the negative control group in antihy-perlipidemic tests. Therefore, we believe that extracts from C. maxima mycelia are rich reservoirs of antioxidant and antihyperlipidemic activities.