The Special Collections Department of the College of Charleston is located on the third floor of the Marlene and Nathan Addlestone Library. The primary mission of Special Collections is to evaluate, acquire, organize, preserve, and make available rare printed and archival materials. Its holdings include the College archives, rare books, and manuscripts.

Special Collections is home to over 500 separate manuscript collections that vary in size from a single item to collections over 400 linear feet. The largest collections are the College of Charleston Archive, the Spoleto Festival Archive, the Jewish Heritage Collection (including the William A. Rosenthall Judaica Collection and Papers), the L. Mendel Rivers Collection, and the Burnet R. Maybank Senatorial Papers. All cataloged manuscript collections are available for public viewing during normal business hours; however, certain restrictions may apply for rare or fragile materials. Additionally, Special Collections houses a number of other non-book collections including the World War I and II poster collections, the South Carolina map collection, the Middleton Family artwork, and the artwork and photographs of naturalist John Henry Dick.

Special Collections houses roughly 35,000 cataloged volumes that include but are not limited to the John Henry Dick ornithology collections, the Colonial Library of Ralph Izard, the Mitchell King Library, the Wendell Levi Library, the Staats Book Arts collection, the Grimke collection of nineteenth century pamphlets, the Derrydale Press collection, the Dr. L.A. Frampton Library, the John Mackenzie Library, the College of Charleston's antebellum Library, the James Warley Miles Library, and the library of the College of Charleston's Chrestomathic Society.