Type 2 diabetes mellitus and other chronic cardio-metabolic conditions are significant contributors to the large disparities in life expectancy between Indigenous and non-Indigenous Australians. Type 2 diabetes is more prevalent from a young age among Indigenous Australians and is often preceded by a cluster of risk factors, including central obesity, dyslipidaemia, albuminuria and socio-economic disadvantage. Management of type 2 diabetes in Australian Indigenous peoples can be challenging in the setting of limited resources and socio-economic disadvantage. Key strategies to address these challenges include working in partnership with patients, communities and primary healthcare services (PHC, Aboriginal community controlled and government services) and working in a multidisciplinary team. Population prevention measures are required within and beyond the health system, commencing as early as possible in the life course.