© 2021 Informa UK Limited, trading as Taylor & Francis Group.The purpose of this study was to investigate and compare the antioxidant and cytotoxic activities of Sarcosphaera crassa and Tricholoma terreum extracts. Phenolic compounds analysis of both mushroom extracts has been carried out by HPLC. Antioxidant activities of the extracts were tested by using in vitro assays. The cytotoxicity of extracts on HT-29 cell line were determined by the WST assay. The total phenolic and total flavonoid contents of T. terreum extracts were higher than those S. crassa. Also, we detected that T. terreum extracts had higher total antioxidant activity and scavenging ability on DPPH radicals than S. crassa extracts. However, the T. terreum methanol extracts showed 27% cytotoxic effect in HT-29 cell line whereas the ethanolic extracts of S. crassa showed cytotoxicity 45%. These results indicate that both mushroom extracts have considerable cytotoxic and antioxidant properties and may be utilized as a promising source of therapeutics.