Docetaxel is widely used in the treatment of non-small cell lung cancer. Fungal immunomodulatory proteins of Flammulina velutipes (FIP- fve ) and Ganoderma tsugae (FIP- gts ) possess immunomodulatory and anti-cancer effects. The abilities of FIP- fve and FIP- gts to protect against docetaxel-induced adverse effects were investigated. FIP- gts , but not FIP- fve , reversed docetaxel-induced decrease in white blood cells (WBCs). On haematoxylin and eosin (H & E), FIP- fve and FIP- gts reduced docetaxel-induced empty vacuoles in bone marrow and damage to small intestinal mucosa. On 3D micro-CT analysis, FIP- fve and FIP- gts significantly reversed docetaxel-induced decreases in percent bone volume (BV/TV), trabecular number (Tb.N) and bone surface density (BS/TV) in mice. Moreover, monocyte chemoattractant protein-1 (MCP-1) production and mRNA expressions induced by docetaxel in A549 cells were diminished by FIP- fve and FIP- gts . Thus, FIP- fve and FIP- gts have the potential to mitigate docetaxel-induced adverse effects in patients undergoing chemotherapy and to serve as novel therapeutic protective agents.