Natural products play a vital role in human health because people find that they can reduce the incidence of many diseases, such as cancer and cardiovascular diseases. Therefore, researchers have developed many effective techniques for screening and separating active compounds from natural products. High‐speed countercurrent chromatography is a unique unsupported liquid–liquid chromatography technology that has been widely used in the separation of natural products. In this paper, the research progress of screening and separating active components from natural products by combining high‐speed countercurrent chromatography technology with other technologies is reviewed from two aspects: pre‐column activity assay and post‐column activity assay. The purpose of this paper is to provide some theoretical support for the screening and separation of natural active compounds by high‐speed countercurrent chromatography. I hope that the contents summarized in this paper can provide more basis for the development of screening and separation of natural active compounds to realize large‐scale preparation.