Photochromic polymers are able to respond to light giving reversible variations of their structure and conformation which, in turn, are accompanied by variations of their physical and chemical properties. This paper describes the photochromic behaviour of poly(α-amino acid)s containing azobenzene and spiropyran groups in the side chains, and illustrates the most significative examples of their photoresponse effects. Experimental findings provide evidence that the molecular and supramolecular structure of these polypeptides can be photomodulated using the photosensitive side chains as effectors. The extent and the kind of photoresponse, including photoinduced coil α-helix transitions, photostimulated aggregation/disaggregation processes, reversible variations of viscosity and solubility, were found to depend on polymer and environment conditions. Interpretative models of the photoresponse effects indicate that photochromic poly(α-amino acid) systems actually behave as amplifiers and transducers of the primary photochemical event occurring in the side chains, and therefore may be promising materials for application in optical technology.