AbstractThe increasing knowledge about natural functional fibrils has triggered the interest in synthetic or engineered fibrils. Naturally occurring amyloid fibrils (functional and pathogenic) have been analyzed for many years at different structural levels. Engineered fibrils are structurally similar to natural fibrils and the main sub-structural feature of amyloids is characterized by cross-beta structure stabilizing the fibril formation. However, a number of peculiarities exist comparing natural and engineered fibrils that may affect their analysis, especially in spectroscopic and scattering methods. For this reason, several methods that are commonly used for natural fibril analysis are presented and particularities for their application in the characterization of engineered fibrils are described. In addition, the understanding about structure–function relation of fibrils studied in the different research areas may mutually improve when using the same analytical approaches for natural and engineered fibrils.