Estimation of the structure-function activity of amyloids originated from natural sequences is a challenging task: Unlike other highly ordered proteinaceous systems, the amyloid state is a misfolded state. Moreover, polymorphism is a key feature of amyloid fibrillar structures, due to their assembly process and surrounding conditions. Glucagon, in particular, was shown to form several polymorphs, depending on the local microenvironment at the early stages of the protofibril assembly, reflecting that the fibrils do not reach singular global energy minimum. Yet, all polymorphs consist of common features such as -sheet assembly in which the strands are spread and oriented in juxtaposed to each other in antiparallel fashion. In respect to polymorphism, although may slightly differ at the mature fibrillar level, the cross- fashion remains dominant.