Phytoremediation is an essential technique for mines' ecological restoration. Modifiers addition can alleviate the stress of heavy metals to plants and enhanced remediation efficiency. Herein, spent mushroom compost (SMC) and calcium carbonate (CaCO3) were added to lead-zinc mine tailings to reveal the mechanism of Macleaya cordata adaptive to heavy metals stress. Pot experiments were conducted in 100% tailing (T), 90% tailing + 5% SMC + 5% CaCO3 (T+), and 100% natural soil (NS). The results indicate that SMC and CaCO3 amendments could improve the structure and fertility of tailings, and promote the growth of M. cordata, increase the content of heavy metals accumulated in plants, enhance the synthesis of chlorophyll and increas the content of soluble protein in leaves; enhance the activities of antioxidase, that can protectcelluar components from oxidative damage. Moreover, most of Pb, Zn, and Cd existed in the cell wall and soluble components, adding SMC and CaCO3 could promote the conversion of Pb, Zn, and Cd to chemical forms with less toxicity and migratory capability. The results of transmission electron microscopy (TEM) and Fourier transform infrared spectrometer (FTIR) showed that SMC and CaCO3 could protect the structural integrity of cells and increase the contents of –OH, –COOH functional groups that can bind to heavy metals in cells. The addition of SMC and CaCO3 can alleviate the stress of heavy metals on M. cordata, enhancing its adaptability to heavy metals and phytoremediation capacity.