Phellinus baumii, a white-rot fungus, has been used for centuries as folk medicine in China, Japan, and Korea. This study aimed to evaluate the in vitro anti-diabetic, and anti-cholinesterase, and in vivo anti-inflammatory effects of the fruiting bodies of P. baumii. The methanol (ME) and hot water (HE) extracts (2.0 mg/mL) of P. baumii fruiting bodies suppressed α-amylase activity, exactly 61.33%, and 65.00%, respectively; of note, acarbose, the positive control, inhibited 93.33% of the α-amylase activity. Moreover, the ME and HE (2.0 mg/mL) inhibited 89.67% and 91.00%, respectively, of the activity of α-glucosidase activity, whereas the same concentration of acarbose suppressed 84.67% of the α-glucosidase activity. The ME and HE (1.0 mg/ mL) also inhibited 96.05% and 94.58%, respectively, of the acetylcholinesterase (AChE) activity; galanthamine, the positive control, led to an inhibition of 81.12%. The butyrylcholinesterase (BChE) activity was also inhibited by ME and HE (1.0 mg/mL; 91.05% and 82.27%, respectively); of note, the same concentration of galanthamine suppressed 81.12% of the BChE activity. The production of NO in LPS-induced RAW 264.7 macrophages was significantly suppressed by both ME and HE treatments. Importantly, the carrageenan-activated rat hind-paw edema was significantly reduced 2–6 h after ME administration (50 mg/mL). Taken together, the results suggest that the fruiting bodies of P. baumii have α-amylase, α-glucosidase, α-cholinesterase, and antiinflammatory activities, and, therefore, may be good natural sources for the promotion of human health.