Abstract: Traditional Chinese medicines (TCMs), with its rich historical legacy and demonstrated efficacy in treating chronic non-communicable diseases, particularly in addressing cancer, cardiovascular diseases, diabetes, and chronic respiratory diseases, presents unique challenges for scientific investigation due to its complex chemical composition and poorly understood mechanisms of action. This review systematically examines the evolution of target fishing technology, evaluates established target identification technology and ligand fishing technology in TCMs research, and synthesizes recent advancements in applying these methodologies to elucidate the therapeutic mechanisms of TCMs for major chronic diseases, with special emphasis on component-target interactions. By providing a critical analysis of current applications and future directions, this work aims to advance the integration of target fishing technologies into modern TCMs research and establish a robust framework for mechanistic studies in this field.