Adolescent refugees resettling in Australia are a vulnerable and marginalised population. Dedicated research to help better understand their health-care needs remains scarce. There are multiple complexities which may deter health professionals from conducting research with this population. Health-care system barriers, such as lack of adolescent- and refugee-specific health-care services, complicate comprehensive data collection. Limited investigator knowledge pertaining to culturally appropriate research in a population with limited English proficiency or a history of trauma can have an impact on adolescent participation and retention in research studies. Additional ethical and legal issues relating to adolescent consent and confidentiality, which include suicidality and physical or sexual abuse, can arise during research and cause potential harm to adolescents if not managed appropriately. This article highlights current knowledge and understanding relating to these issues along with recommendations to address barriers and safeguard adolescents, with the aim of promoting high-quality research that will benefit resettling adolescent refugees.