This article explores links between arts, health, and wellbeing for diverse First Nations and non-Indigenous peoples living in the very remote Barkly Region of the Northern Territory in Australia. The article stems from a major 3-year study of the Barkly arts sector conducted in partnership with Barkly Regional Arts and Regional Development Australia Northern Territory. Key findings relate to an arts-health ecology evident in the region, the interdependence between artists' own health and their arts activity, the value of arts spaces as places of safety and refuge, and the potential of the arts to promote cultural and intercultural healing and development. We discuss these findings in the context of relevant literature and make suggestions for future arts-health and wellbeing related research, policy and practice in rural and remote contexts. This study employed an ecological mixed-methods research design, including quantitative and qualitative survey and interview data collection as well as collaborative, data-driven thematic analysis. The ecological approach was used to map a variety of creative practices through a broad range of art forms. Commercial, amateur and subsidised art and creative practices were included in this study and represented the multicultural population of the Barkly Region (both First Nations and non-Indigenous peoples). Arts and creativity in the region were recognized as a complex ecology that saw individuals, businesses, organisations and government working in different ways to sustain culture and contribute to social and economic development. Research participants from diverse cultural backgrounds recognised health and wellbeing benefits of arts and creative activity. Arts participation and engagement were reported to have intrinsic individual health and wellbeing effects such as mental health and mindfulness, emotional regulation, enjoyment, and relief of physical and emotional pain and stress alongside promoting spiritual connection to self, culture and community. The study indicates that the arts can also shape powerful determinants of health and wellbeing such as employment, poverty, racism, social inclusion, and natural and built environments. Barkly arts-health ecology featured extensive involvement from health and human service and arts organisations, which provided a strong foundation for inclusive, healing and holistic regional development. This study has outlined how arts and creative activity contribute to holistic regional development in the Barkly desert region, an area with a high percentage of First Nations peoples. Arts and creative activity were reported to have intrinsic health and wellbeing effects for individuals, which included mental health and mindfulness, emotional regulation, enjoyment, and relief of physical and emotional pain and stress as well as promoting spiritual connection to self, others and environment. Arts activities were also seen to shape powerful determinants of health and wellbeing such as employment, poverty, racism, social inclusion, and natural and built environments.