There are approximately 130 reported medicinal effects of mushrooms. We investigated the anti-inflammatory effects of hot-water extracts of 66 wild and cultivated fungi species (both edible and poisonous) by analyzing inhibition of platelet aggregation and interleukin (IL)-8 gene expression induced by sodium arachidonate (A-Na), platelet-aggregating factor (PAF), and adenosine diphosphate (ADP). All species exhibited inhibitory effects: 38.3%–98.1%, 37.3%–96.8%, and 41.0%–96.6% species inhibited platelet aggregation induced by A-Na, PAF, and ADP, respectively, while 17.0%–97.0% inhibited IL-8 expression. Gyromitra esculenta showed the highest inhibition rate in all assays. High inhibition (≥80%) of A-Na-, PAF-, and ADP-induced platelet aggregation was observed in 29 (43.9%), 29 (43.9%) and 31 (47.0%) species, respectively. Half (33) of the species exhibited high inhibition of IL-8 expression. Four (6.1%), five (7.6%), and seven (10.6%) species exhibited inhibition rates of < 50% for A-Na-, PAF-, and ADP-induced platelet aggregation, while nine (13.6%) exhibited low inhibition of IL-8 expression. The majority (87.5%–100%) of poisonous species exhibited high inhibition. Our findings suggest that anti-inflammatory effects are universal among fungi, with poisonous species showing particular potential as raw materials for drug discovery. It can be inferred that many fungi contain universal or pleiotropic compounds with anti-inflammatory activities.