Cultivated fruiting body of Grifola frondosa is a culinary and medicinal mushroom. In this study, we investigated its functional food value. Extracts of its fruiting body afforded known compounds, glycerides (1 and 2), sterols (3–5), a glucosylceramide (6), a α-glucose dimer (7), a phospholipid (8) and α-glucans as elucidated by spectroscopic methods. This is the first report of compounds 2, 5 and 8 from the fruiting body of G. frondosa. Most of the pure isolates showed antiinflammatory and antioxidant activities as demonstrated by inhibitions of cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation (LPO), respectively. Compounds 1, 4, and 5 from this mushroom inhibited COX enzymes at 100 µg/mL similar to aspirin, naproxen and ibuprofen, the non-steroidal antiinflammatory drugs (NSAIDs) used as controls in the assays.