Polypeptoids have attracted a lot of atteSDntion because of their unique structural characteristics and special properties. Polypeptoids have the same main chain structures to polypeptides, making them have low cytotoxicity and excellent biocompatibility. Polypeptoids can also respond to external environmental changes by modifying the configurations of the side chains. The external stimuli can be heat, pH, ions, ultraviolet/visible light and active oxygen or their combinations. This review paper discussed the recent research progress in the field of stimulus-responsive polypeptoids, including the design of new stimulus-responsive polypeptoid structures, controlled actuation factors in response to external stimuli and the application of responsive polypeptoid biomaterials in various biomedical and biological nanotechnology, such as drug delivery, tissue engineering and biosensing.