Natural active products (NAPs) are derived from chemical substances found in nature that have biological activity and medicinal potential. Screening and revealing the protein targets of NAPs is an indispensable link in the pharmacological and toxicological understanding of NAPs. Proteins are the main factors executing cell functions, and cells rely on the function of proteins to complete various activities in the life cycle. The important mechanism of action of drugs is to regulate cell biological activities by interacting with proteins and other macromolecules. At present, the classic way to screen protein targets is based on the molecular label tracing method, which has a long cycle and changes the molecular structure and pharmacological effects of NAPs. Due to the shortcomings of molecular labelling methods, in recent years, scientists have tried to develop a variety of label-free protein target identification methods for NAPs and have made a certain amount of progress. This article reviews the current protein target identification methods for NAPs with the aim of providing a reference for research on NAP protein targets.