Approximately 370–500 million Indigenous people live worldwide. While Indigenous peoples make up only 5% of the world’s population, they account for 15% of the extreme poor and have life expectancy that is 20 years shorter than that of non-Indigenous people. Access to healthcare has been identified as an important social determinant of health and key driver of health outcomes. Indigenous populations often face barriers to accessing healthcare including living in remote areas, lacking financial resources, and having cultural differences. Telehealth, the utililzation of any synchronous modality, including phone, video, or teleconferencing technology used to support the provision of long-distance health care and health education, is a feasible and cost-effective treatment delivery mechanism that has successfully addressed access barriers faced by vulnerable populations globally, however, few studies have included indigenous populations and the application of this technology to improve physical and mental health outcomes. This systematic review aims to identify trials that were conducted among Indigenous adults, and to summarize the components of interventions that have been found to effectively improve the health of Indigenous peoples. The PRISMA guidelines for reporting of systematic reviews were followed in preparing this manuscript. Studies were identified by searching PubMed, Scopus, and PsychInfo databases for clinical trial articles on Indigenous peoples and mental and physical health, published between January 1, 1998 and December 31, 2018. Eligibility criteria for determining studies to include in the analysis were as follows: (I) ≥18 years of age; (II) indigenous peoples; (III) any technology-based intervention; (IV) studies included at least one of the following mental health (depression, post-traumatic stress disorder, suicide) and physical health (mortality, blood pressure, hemoglobin A1C, cholesterol, quality of life) outcomes; (V) clinical trials. A total of 2,662 articles were identified and six were included in the final review based on pre-specified eligibility criteria. Three were conducted in the United States, one study was conducted in Canada, and two were conducted in New Zealand. Study sample sizes ranged from 20 to 762, intervention delivery times ranged from three to 20 months and utilized telephone, internet and SMS messaging as the type of technology. There is a paucity of evidence on the use of telehealth programs to increase access to chronic disease programs in Indigenous populations. This review highlights the importance of culturally tailoring programs despite the modality in which they are delivered, and recommends telephone-based delivery facilitated by a trained health professional. Telehealth has great promise for meeting the health needs of highly marginalized Indigenous populations around the world, however, at this point more research is needed to understand how best to structure and deliver these programs for maximum effect.