The museum has several collections of prehistoric Native American artifacts, which illustrate aspects of the daily and ceremonial lives of the indigenous peoples who lived in southeastern Missouri from 13,500 B.C. to 1400 A.D.
Highlights of the archaeological collections include:
- One of the largest collections of ceramic conch shell effigies in North America
- An outstanding collection of whole vessels from southeastern Missouri
- A comprehensive collection of lithics (stone tools) dating from the Paleo-Indian to the Late Mississippian periods.
The museum's archaeological display features representative artifacts from the Thomas Beckwith Collection, which contains nine hundred whole ceramic vessels and effigy fragments plus approximately two thousand lithics. Most of the objects in the collection were excavated by Thomas Beckwith at the end of the 19th and beginning of the 20th centuries from mounds on his property in southeast Missouri.
In 1913, Beckwith donated his collection to the Third District Normal School, the predecessor to Southeast Missouri State University. Since 1976, the collection has been housed in the Southeast Missouri Regional Museum. Today the collection provides unique insights into the culture and lives of prehistoric Native peoples of this region.
The museum also has a number of historic and contemporary Native American objects including Kachina dolls, Southwestern blankets, baskets, and examples of decorative beadwork.