Background Globally, unhealthy alcohol use disrupts the wellbeing of communities and is a leading cause of premature death and disability. Primary care services help individuals with the full spectrum of unhealthy alcohol use. Incorporating First Nations approaches alongside standard evidence-based (Western) approaches, may improve intervention acceptability and effectiveness. Aims To identify peer-reviewed studies of outpatient alcohol treatments for First Nations peoples of Australia, New Zealand, USA, and Canada; explore the role of culture in alcohol care delivered in 11 Aboriginal Community Controlled Health Services (ACCHSs); and assess prescription rates of alcohol relapse prevention medicines in 22 ACCHSs over 12-months and identify associated factors. Methods A systematic review summarises scope and nature of literature including culture underpinning interventions (Western; First Nations culture; bicultural). A qualitative analysis of interview data with First Nations ACCHS staff investigates the role of culture in alcohol care using a novel analytic method. Routinely collected data on prescription rates of relapse prevention medicines were analysed, and (using logistic regression) associated client or service factors. Results and discussion Cultural and bicultural interventions were described for First Nations peoples in New Zealand, USA and Canada, but not Australia. US-based studies included trials of relapse prevention medicines. The qualitative study highlighted a comprehensive bicultural model of alcohol care. Prescription rates were low across the 22 ACCHSs. Prescription was more likely for clients screened with AUDIT-C, who were male, middle age, and attended an urban service. Conclusion Internationally, First Nations culture and healing traditions have played a role in primary care treatment for unhealthy alcohol use alongside Western approaches. This research describes use of a bicultural approach in Australian ACCHSs.