Background Mushrooms include a wide variety of bioactive compounds that have been linked to therapeutic and nutritional benefits, making them a potential source of new medications and functional foods. Objective The goal of this study is to offer a complete overview of the mushroom's modulatory effects on inflammatory signaling pathways, which leads to the inhibition of inflammation in various types of immune cells and animal models. Methods This study reviewed the inhibitory effects of mushrooms on the inflammation process through the modulation of the pro-inflammatory mediators and associated signaling pathways. A literature search in PubMed and Google Scholar was conducted for the relevant original research and review articles on the anti-inflammatory effects of mushrooms. Related articles published in English were selected, studied and discussed. Results As revealed by the selected articles, bioactive molecules which include peptides, polysaccharides, terpenes, sterols, fatty acids, and phenols have been extracted from the powder, concentrate, and different solvent extracts of edible mushrooms. These bioactive molecules have shown significant efficacy in inhibiting the major pro-inflammatory biomarkers and associated pathways in in vivo and in vitro settings. Conclusion This review demonstrated that mushrooms significantly inhibit the production of pro-inflammatory mediators and can be developed for clinical use as anti-inflammatory agents. Further research is required to establish the comparative efficacy between mushrooms and NSAID especially in the in vivo inhibitory activity against the production of cyclooxygenase and pro-inflammatory cytokines.