Background The growing incidence of mental ill-health in health professionals, including doctors, is a global concern. Although a large body of literature exists on interventions that offer support, advice and/or treatment to sick doctors, it has not yet been synthesised in a way that takes account of the complexity and heterogeneity of the interventions, and the many dimensions (e.g. individual, organisational, sociocultural) of the problem. Objectives Our aim was to improve understanding of how, why and in what contexts mental health services and support interventions can be designed to minimise the incidence of doctors’ mental ill-health. The objectives were to review interventions to tackle doctors’ mental ill-health and its impact on the clinical workforce and patient care, drawing on diverse literature sources and engaging iteratively with diverse stakeholder perspectives to produce actionable theory; and recommendations that support the tailoring, implementation, monitoring and evaluation of contextually sensitive strategies to tackle mental ill-health and its impacts. Design Realist literature review consistent with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards quality and reporting standards. Data sources Bibliographic database searches were developed and conducted using MEDLINE (1946 to November week 4 2017), MEDLINE In-Process and Other Non-indexed Citations (1946 to 6 December 2017) and PsycINFO (1806 to November week 2 2017) (all via Ovid) and Applied Social Sciences Index and Abstracts (1987 to 6 December 2017) (via ProQuest) on 6 December 2017. Further UK-based studies were identified by forwards and author citation searches, manual backwards citation searching and hand-searching relevant journal websites. Review methods We included all studies that focused on mental ill-health; all study designs; all health-care settings; all studies that included medical doctors/medical students; descriptions of interventions or resources that focus on improving mental ill-health and minimising its impacts; all mental health outcome measures, including absenteeism (doctors taking short-/long-term sick leave); presenteeism (doctors working despite being unwell); and workforce retention (doctors leaving the profession temporarily/permanently). Data were extracted from included articles and the data set was subjected to realist analysis to identify context–mechanism–outcome configurations. Results A total of 179 out of 3069 records were included. Most were from the USA (45%) and had been published since 2009 (74%). More included articles focused on structural-level interventions (33%) than individual-level interventions (21%), but most articles (46%) considered both levels. Most interventions focused on prevention, rather than treatment/screening, and most studies referred to doctors/physicians in general, rather than to specific specialties or career stages. Nineteen per cent of the included sources provided cost information and none reported a health economic analysis. The 19 context–mechanism–outcome configurations demonstrated that doctors were more likely to experience mental ill-health when they felt isolated or unable to do their job, and when they feared repercussions of help-seeking. Healthy staff were necessary for excellent patient care. Interventions emphasising relationships and belonging were more likely to promote well-being. Interventions creating a people-focused working culture, balancing positive/negative performance and acknowledging positive/negative aspects of a medical career helped doctors to thrive. The way that interventions were implemented seemed critically important. Doctors needed to have confidence in an intervention for the intervention to be effective. Limitations Variable quality of included literature; limited UK-based studies. Future work Use this evidence synthesis to refine, implement and evaluate interventions. Study registration This study is registered as PROSPERO CRD42017069870. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 19. See the NIHR Journals Library website for further project information.