Pleurotus pulmonarius var. stechangii is a culinary-medicinal mushroom commonly cultivated in subtropical countries in Asia. In this study, the in vitro antixanthine oxidase, antihyperglycemic, and in vivo anti-inflammatory activities of a methanol extract (ME) of P. pulmonarius var. stechangii fruiting bodies were evaluated. The xanthine oxidase inhibitory activity of the ME of P. pulmonarius var. stechangii was lower than that of allopurinol, a xanthine oxidase inhibitor used as a positive control. Eleven phenolic compounds were identified from the fruiting bodies of P. pulmonarius var. stechangii by HPLC analysis. The inhibitory effects of ME on α-amylase and α-glucosidase were moderate and lower than that of acarbose, a positive control. The ME inhibited the production of nitric oxide (NO) and nitric oxide synthases (iNOS) protein expression in lipopolysaccharide-induced RAW 264.7 macrophages. It also exhibited an inhibitory effect on carrageenan-induced hind paw edema in a rat model. Taken together, our experimental results demonstrated that the fruiting bodies of P. pulmonarius var. stechangii might be a good natural source to promote human health through its antixanthine oxidase, antihyperglycemia, and anti-inflammatory activities.