ScopeParticulate matter (PM) contains toxic organic matter and heavy metals that enter the entire body through blood flow and may cause mortality. Ganoderma formosanum mycelium, a valuable traditional Chinese medicine that has been used since ancient times, contains various active ingredients that can effectively impede inflammatory responses on murine alveolar macrophages induced by PM particles.Methods and ResultsAn experimental study assessing the effect of G. formosanum mycelium extract's water fraction (WA) on PM‐exposed murine alveolar macrophages using ROS measurement shows that WA reduces intracellular ROS by 12% and increases cell viability by 16% when induced by PM particles. According to RNA‐Sequencing, western blotting, and real‐time qPCR are conducted to analyze the metabolic pathway. The WA reduces the protein ratio in p‐NF‐κB/NF‐κB by 18% and decreases the expression of inflammatory genes, including IL‐1β by 38%, IL‐6 by 29%, and TNF‐α by 19%. Finally, the identification of seven types of anti‐inflammatory compounds in the WA fraction is achieved through UHPLC‐ESI‐Orbitrap‐Elite‐MS/MS analysis. These compounds include anti‐inflammatory compounds, namely thiamine, adenosine 5ʹ‐monophosphate, pipecolic acid, L‐pyroglutamic acid, acetyl‐L‐carnitine, D‐mannitol, and L‐malic acid.ConclusionsThe study suggests that the WA has the potential to alleviate the PM ‐induced damage in alveolar macrophages, demonstrating its anti‐inflammatory properties.