Background: The Communicate Study is a partnership project which aims to transform the culture of healthcare systems to achieve excellence in culturally safe care for First Nations people. It responds to the ongoing impact of colonisation which results in First Nations peoples experiencing adverse outcomes of hospitalisation in Australia’s Northern Territory. In this setting, the majority of healthcare users are First Nations peoples, but the majority of healthcare providers are not. Our hypotheses are that strategies to ensure cultural safety can be effectively taught, systems can become culturally safe and that the provision of culturally safe healthcare in first languages will improve experiences and outcomes of hospitalisation. Methods: We will implement a multicomponent intervention at three hospitals over 4 years. The main intervention components are as follows: cultural safety training called ‘Ask the Specialist Plus’ which incorporates a locally developed, purpose-built podcast, developing a community of practice in cultural safety and improving access to and uptake of Aboriginal language interpreters. Intervention components are informed by the ‘behaviour change wheel’ and address a supply–demand model for interpreters. The philosophical underpinnings are critical race theory, Freirean pedagogy and cultural safety. There are co-primary qualitative and quantitative outcome measures: cultural safety, as experienced by First Nations peoples at participating hospitals, and proportion of admitted First Nations patients who self-discharge. Qualitative measures of patient and provider experience, and patient-provider interactions, will be examined through interviews and observational data. Quantitative outcomes (documentation of language, uptake of interpreters (booked and completed), proportion of admissions ending in self-discharge, unplanned readmission, hospital length of stay, costs and cost benefits of interpreter use) will be measured using time-series analysis. Continuous quality improvement will use data in a participatory way to motivate change. Programme evaluation will assess Reach, Effectiveness, Adoption, Implementation and Maintenance (‘RE-AIM’). Discussion: The intervention components are innovative, sustainable and have been successfully piloted. Refinement and scale-up through this project have the potential to transform First Nations patients’ experiences of care and health outcomes. Trial registration: Registered with ClinicalTrials.gov Protocol Record 2008644.