In addition to natural history exhibits, the main museum in Springfield focuses on the state's cultural and artistic heritage.

Exhibits include local fossils and mining, household displays from different historic periods, dioramas of Native American life, archaeological and ethnographic artifacts, and a collection of glass paperweights.

The headquarters museum is located on Spring and Edwards Streets, one block southwest of the Illinois State Capitol, in Springfield.

Exhibits include hands-on displays, dioramas, photos and artifacts that depict area cultures from the Ice-Age to the 19th century.

The museum grounds comprise 230 acres (0.93 km2) including the Eveland Village, the excavated remains of three early Native American buildings.

The gallery is located in the 1850 Norton Building, which was originally used to house grain, a supply store, and a dormitory for canal crews.

The Illinois State Museum is charged by state law with the responsibility "to collect and preserve objects of scientific and artistic value, representing past and present fauna and flora, the life and work of man, geological history, natural resources, and the manufacturing and fine arts; to interpret for and educate the public concerning the foregoing.