This book constitutes the thoroughly refereed proceedings of the 15th International Conference on Metadata and Semantic Research, MTSR 2021, held as a virtual event in November-December 2021.  The 27 full and 7 short papers presented were carefully reviewed and selected from 92 submissions. The papers are organized in the following topical sections: metadata, linked data, semantics and ontologies - general session, and track on agriculture, food and environment; track on open repositories, research information systems and data infrastructures; track on knowledge IT artifacts (KITA) and decentralized applications, blockchains and P2P systems, and general session; track on digital humanities and digital curation, and general session; track on digital libraries, information retrieval, big, linked, social and open data; track on european and national projects, and general session; track on cultural collections and applications, and general session.