Abstract Indole[2,1‐ a ]isoquinoline structures are widely present in many drug molecules and natural product molecules. Its derivatives have a wide range of physiological and pharmacological activities such as antibacterial, antiviral, anti‐tumor,anti‐cytostatic,anti‐venom, and as an inhibitor of tubulin polymerization properties. They are also important intermediates in organic synthesis and structural units in drug synthesis. Therefore, indole[2,1‐ a ]isoquinoline compounds have great application value in the pharmaceutical field. The study of its synthesis methods has also become an important research field of organic synthesis. At present, chemists have developed many efficient methods for synthesizing indole[2,1‐ a ]isoquinoline derivatives. Thispaper reviews the research progress in the synthesis methods and application of indole[2,1‐ a ]isoquinoline compounds in recent years, and representative examples and reaction mechanisms are discussed.