Indigenous peoples have inhabited Appalachia for over 12,000 years, developing diverse cultures and complex societies. The Cherokee, Shawnee, Creek, Chickasaw, and Choctaw nations thrived in the region, engaging in trade and agriculture before European contact. European colonization brought disease, displacement, and cultural suppression to indigenous communities. Despite these challenges, indigenous peoples in Appalachia have shown resilience, working to preserve their languages, traditions, and connection to the land while addressing contemporary issues of sovereignty and environmental justice.