Feedstocks that have high protein contents, such as soy protein, are promising materials for extensive polyol and polyurethane (PU) applications, such as foams, films, and coatings, due to the characteristic structures and properties of proteins. Currently, most research has been focused on the direct use of these protein-based feedstocks in combination with polymers for PU production. Although proteins have multiple reactive functional groups, such as amino and carboxyl groups, reports on the modification of protein-based feedstocks for the production of liquid polyols are limited. This chapter reviews sources, compositions, structures, and processing of protein-based feedstocks; synthetic methods and properties of protein-based polyols; and performance and applications of the derived PUs.