In this study, the antioxidant and anti-inflammatory effects of methanol extract (ME) and hot water extracts (HE) from the fruiting bodies of Ganoderma applanatum were investigated. The 1,1-diphenyl-2-picryl-hydrazy (DPPH) radical scavenging activity of 2.0 mg/mL ME (94.83%) was comparable to that of butylated hydroxytoluene (96.97%), the reference standard. The hydroxyl radical scavenging activities of ME and HE were similar to that of BHT at 2.0 mg/mL, whereas lipid peroxidation activity of the ME and HE were significantly lower than that of BHT. High-performance liquid chromatography analysis showed that the G. applanatum fruiting bodies contained nine phenolic compounds, which might contribute to antioxidant and anti-inflammatory activities. The survival rate of RAW 264.7 macrophages treated with 2.0 mg/mL ME and HE were 65.23 to 68.12% at 2.0 mg/mL, thereby indicating that the extracts were slightly cytotoxic at the concentration tested. The extracts also inhibited the nitric oxide (NO)-mediated expression of inducible nitric oxide synthase (iNOS) protein in lipopolysaccharide-induced RAW 264.7 macrophages and carrageenan-induced paw edema in rats. The study results demonstrated that the fruiting bodies of G. applanatum possessed good antioxidant and anti-inflammatory activities, which might be used to develop novel anti-inflammatory agents.