Abstract: Objective In the flotation separation of copper-lead sulfide ores, due to the close coexistence between chalcopyrite and galena, complex interweaving relationship, similar natural floatability, and the activation effect of copper ions on galena, the issue of copper-lead separation has remained a key and difficult point in the field of mineral processing up to now. Efficient and selective galena inhibitors are the key to solving the problem of copper-lead separation. Method This article introduces the macromolecular organic inhibitors of galena and their mechanisms of action from the perspectives of natural macromolecules and synthetic macromolecules respectively. At the same time, it analyzes the future development direction of macromolecular organic inhibitors of galena in combination with reality. Result Macromolecular organic inhibitors mainly exert physical adsorption, chemical adsorption, hydrogen bond adsorption and competitive adsorption on the surface of galena through functional groups such as hydroxyl, alkyl, carboxyl and phenolic hydroxyl groups in their molecular structure, thereby enhancing the hydrophilicity of the galena surface or hindering its interaction with collectors, achieving selective inhibition. Although certain research achievements have been made in this field both at home and abroad, the problem of copper-lead separation in actual mineral processing production has not been widely improved. The main crux lies in the lack of systematicness and depth in the mechanism research of natural macromolecular inhibitors, and the regulation laws of synthetic inhibitors under the influence of multiple factors in pulp are still unclear. Conclusion In the future, the theoretical system of macromolecular organic inhibition should be further improved, and efforts should be made to develop new, efficient and environmentally friendly organic inhibitors. This is the key direction for promoting the progress of copper-lead separation technology.