Abstract Chemical investigation on the peels of the cultivated edible mushroom Wolfiporia cocos led to the identification of 13 diterpenes and 4 steroids, including two new abietane diterpenes (1 and 2) and one new pregnane steroid (14). Structures of new compounds were determined by analysis of NMR, MS, and electronic circular dichroism (ECD) data. All compounds were evaluated for cytotoxicity (K562 and HepG2), antimicrobial and anti-inflammatory activity. Compounds 15, 17 showed strong cytotoxicity on K562 cells with the IC50 values of 5.4 and 7.5 μM, respectively. Compounds 4, 9 and 17 displayed medium antibacterial activity against Staphylococcus aureus with MICs of 31.3, 48.5 and 12.5 μM, respectively. Compounds 1-10, 14 and 16 showed inhibitory activity on the NO (nitric oxide) release in LPS-induced RAW 264.7 cells with IC50 values at the range of 16.8–75.8 μM. This work confirms the potential of peels of W. cocos in the treatment of infection diseases.