BACKGROUND: Effective and rapid actions are required to achieve global goals for climate change mitigation, and there is an opportunity to ensure that the actions taken are also positive for human health. However, little is known about the relative magnitude of the health co-benefits that can be achieved from mitigation actions, so robust and comprehensive syntheses of the evidence on the nature and effects of relevant actions are required. This paper presents a protocol for an interdisciplinary and cross-sectoral umbrella review of systematic reviews, synthesising modelled and empirical evidence on such actions. METHODS: Nine bibliographic databases will be searched, capturing literature across a wide range of disciplines and sectors. Unique records retrieved by the searches will be screened by two independent reviewers. The quality of all the included systematic reviews will be assessed using A MeaSurement Tool to Assess Systematic Reviews (AMSTAR) 2 critical appraisal tool. Data will be extracted on methodological and thematic characteristics of the reviews, nature of the actions, and their effects on greenhouse gas emission reduction, health, and its determinants, as well as any other reported effects and interactions across different actions. RESULTS: Narrative and quantitative synthesis methods will be used to create a typology of relevant actions, map pathways to their impacts on health, compare the magnitude of health and greenhouse gas (GHG) emission reduction impacts by selected characteristics of the actions and the nature of the evidence, as well as to identify gaps in evidence syntheses. CONCLUSION: This review will identify the most effective actions for global climate change mitigation and health based on the best available scientific evidence.   This protocol has been registered in PROSPERO, Reg No.: CRD42021239292.