Many Indigenous communities around the world are facing a health crisis aggravated by environmental degradation and dispossession. Through community-based participatory research, we examined barriers to land use, declining environmental health and human health implications for the Isga People in west-central Alberta, Canada. Through interviews, land use-and-occupancy and traditional and local knowledge of environmental change was spatially documented. Key concerns including declining wildlife health and water quality were largely attributed to the petroleum and forestry industries. Barriers included the encroachment of industry, agriculture and urban development, and a legacy of state-imposed assimilation policies. Human health concerns were associated with these barriers and environmental degradation along with a loss of connection to land and cultural practices. However, community resilience was also evident in the persistence of land use and cultural revival. Underlying environmental and sociopolitical factors are crucial for the health and wellbeing of the Isga and Indigenous Peoples worldwide.