In 2001, Wiesbaden converted the Villa Clementine into a house of literature. A literature department belonging to the Department of Culture is responsible for the program and management. The establishment of the House of Literature was initiated when the Hessian Publishers and Booksellers Association moved into the second floor of the Villa Clementine in 2000.

The concept is to encourage debate and further reading through literary events and thematic series, to strengthen the feeling for language and sound, rhythm and melody and to sharpen the sense for literary motifs, linguistic images and techniques. Writers read from their latest works and engage in discussion with other authors, literary critics, academics, editors, translators, publishers and the public. The Literaturhaus Villa Clementine is therefore also a meeting place. A café was set up in 2009. With scholarships, guest residencies for international authors in cooperation with the Hessischer Literaturrat e.V. and writing workshops, the house is committed to the sustainable promotion of literature. Following on from the history of the city, where writers such as Fyodor Dostoyevsky have stayed, the focus is on Eastern European literature. The focus, however, is on contemporary German-language literature. As part of the "Wiesbaden reads" series of events, well-known personalities themselves presented selected texts to the public from 2000-09.

Since 2006, the Villa Clementine House of Literature has been dedicated to presenting literature for children and young people. The "Junges Literaturhaus" series in cooperation with the Börsenverein des Deutschen Buchhandels - Landesverband Hessen, Rheinland-Pfalz, Saarland e.V. and Wiesbaden schools is aimed at children and young people. The "Wiesbadener Literaturtage" has been organized by the Literaturhaus Villa Clementine since 2001. Award-winning authors such as Erich Fried, Urs Widmer, Margriet de Moor, Péter Esterházy, Christoph Hein, Monika Maron, Thea Dorn, Eva Demski and Christian Brückner have already acted as hosts, putting together a week-long program according to their wishes and facilitating unusual encounters.

Last but not least, the Literaturhaus Villa Clementine offers literary associations, literary initiatives and bookshops a place for their own program work. It is supported by the Förderverein Literaturhaus Villa Clementine e.V., which was founded in 2002. Since July 2015, the Literaturhaus Villa Clementine has been a member of the network of literature houses.