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Coriolopsis aspera is a medicinal mushroom, it contains a variety of powerful antioxidants and other compounds that help boost immune system and fight certain cancers. This study aims to test the acute toxicity of the ethanolic extract from fruiting masses of Turkey tails (Coriolopsis aspera) in Siss albino mice. Studies were carried out with a fixed dose of 2000, 4000, and 6000 mg/kg body weight through oral administration daily. In terms of behavior and mortality, signs of toxicity were noted after every two hours to 24 hours in an acute toxicity test. The test Swiss albino mice were continued to use the Coriolopsis aspera ethanolic extracts for up to 14 days. The physical, biochemical, hematological parameters of the mice were analyzed and the histopathological of heart, liver, kidney were studied. The results showed that the highest dose used did not cause death or change test animals’ general behavior. All parameters were unaltered throughout the stude. The present study revealed no obvious toxicity in mice treated with Coriolopsis aspera. These results indicate the safety of the oral administration of fruiting masses extract.