Foxtail millet (Setaria italica), an annual grass plant, produces seeds that possess health‐promoting properties owing to its unique protein composition containing a high content of essential amino acids. The mature foxtail seeds mainly consist of proline‐rich, alcohol‐soluble proteins (prolamin) called setarins, comprising about 60% of the total protein, with less content of disulfide cross‐linked proteins than with other cereal and millets. Protein fractionation schemes are an important tool and provide preliminary information on the nature of foxtail proteins for their applications in the field of agriculture, food pharma, and bio‐based materials. Variation in the methods of preparation can influence the composition, structure, and nutritional quality of the protein concentrate. Moreover, foxtail protein or its hydrolysate has shown several bioactive effects that can be explored further for the management of chronic diseases in humans. Additionally, owing to its low cost and excellent functional properties of flour and protein concentrate, foxtail millet can be considered as good candidate for replacing animal protein foods. Furthermore, there is huge potential for successfully developing low‐cost, protein‐rich functional food products helpful in the prevention and management of lifestyle‐related chronic diseases. © 2020 Society of Chemical Industry