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Mushrooms are traditionally used for various medicinal purposes in traditional oriental medicine. The Japanese and Chinese are familiar with the medicinal macro fungus Lentinula edodes (Shiitake mushroom). This study aims to evaluate the role of chemical compounds from L. edodes using network pharmacology and in-vitro studies for management of Obesity. Bioactive compounds in extracts of L. edodes were identified by GC-MS analysis. Compounds were later screened for their drug-like property by Lipinski's rule. In addition, public databases (SEA, STP, Omim and DisGenet) were searched to identify genes associated with selected molecules and obesity, as well as genes that overlap obesity target genes with genes related to L. edodes. Additionally, analysis was performed using Enrichr KG to predict the disease targets of L. edodes. Finally, network was constructed between the overlapping genes and bioactive molecules using Rstudio. Further in-vitro studies were carried out using 3T3-L1 cell line. The genes related to the selected compounds and obesity were identified and overlapped. The disease targets of L. edodes was predicted by enrichment analysis and was found to be linked to obesity. Furthermore, the hub gene was found to be fatty acid amide hydrolase, and the key bioactive compound was hexadecanoic acid methyl ester. The in-vitro cell culture studies confirmed the inhibition of adipogenesis in mushroom extract-treated 3T3-L1 cells and the augmentation of adiponectin. The study suggests that the hub gene fatty acid amide hydrolase might alleviate obesity by inhibiting arachidonoyl ethanolamide signaling, which would enhance the action of fatty acid amide hydrolase and limit appetite in L. edodes extract.