A compositional study was performed on fruiting-body powder of the culinary-medicinal oyster mushroom Pleurotus ostreatus for applications as a nutraceutical/functional food. Carbohydrates (55 g/100 g dry weight [dw]) and proteins (27.45 g/100 g dw, with an in vitro digestibility of 75%) appear to be the major components, but fat content was low (4 g/100 g dw). Pleurotus powder has important micronutrients such as minerals (Fe, Cu, Zn, Mn, Mg, and Co) and ascorbic acid, as well as nonnutrients (i.e., phenolics) with antioxidant potential. A powder-derived aqueous extract had a phenolic compound content of 138 mg/100 g that showed 2,2-diphenyl-1-picrylhydrazyl radical scavenging and inhibition of membrane-lipid peroxidation activities of 58.3% and 61.4%, respectively. The presence of β-1,3-1,6-D-glucans was also demonstrated (1.54 g/100 g). An acute toxicity test proved that Pleurotus powder was safe after oral administration to both male and female mice at a dose of 2000 mg/kg. The combination of rich nutritional composition, bioactivity, and safety in P. ostreatus fruiting-body powder highlights its potential as a nutraceutical agent promoting health and life quality.