<p>Identifying natural products (NPs) targets is of great significance for the study of drug function mechanisms and the discovery of new compounds acting on the targets. Chemical proteomics technologies provide new perspectives, among which activity-based Protein Profiling (ABPP) has attracted much attention as a research hotspot. In this paper, we systematically review the application of various chemical proteomics technologies in natural product target identification, in which the development of ABPP is elaborated in detail, including the traditional biotin-labeled probe technology, the application of bioorthogonal strategy and photoaffinity cross-linking reaction of ABPP (AfBPP) and their advantages and disadvantages. Meanwhile, We also illustrate the joint application of ABPP with other technologies to demonstrate the innovative value of technology integration. Finally, the application examples of ABPP were introduced by categorizing from two perspectives of natural product types and disease research directions, showing the important value and unique advantages of ABPP in NPs target research, such as precisely identifying targets and providing key information for new drug development. However, each chemical proteomics technology still faces various challenges, such as the optimization of ABPP probe design and the control of the effect on the physiological state of the cell, which need to be further improved and perfected in the future to accelerate the drug development.</p>