The largest group of collection manuscripts are written in or provide documentation about Mayan languages. Note that the nomenclature and categorization of this diverse group of indigenous languages can be complex, but included are languages historically spoken in areas that now include parts of Mexico, Guatemala, Honduras, and Nicaragua. These include Maya, Cakchikel, Pocomchi, Kekchi, and others. The collection contains multiple manuscript copies of the Chilam Balam, along with related materials.
Materials from central Mexico include texts in Nahuatl and Otomi.
A small number of manuscripts in the collection relate to North America. These include the now-disputed Wallam Olum, a pictographic manuscript of Lenni Lenape (Delaware) history and mythology compiled by Samuel Rafinesque, and a Huron-Latin-French grammar compiled in the early 18th century by Pierre-Philippe Potier.