Abstract Introduction Increasing collaborative and integrated working between General practice (GP) and Community pharmacy (CP) is a key priority of the UK National Health Service and has been proposed as a solution to reducing health system fragmentation, improving synergies and coordination of care. However, there is limited understanding regarding how and under which circumstances collaborative and integrated working between GP and CP can be achieved in practice and how regulatory, organisational and systemic barriers can be overcome. Methods and analysis The aim of our review is to understand how, when and why working arrangements between GP and CP can provide the conditions necessary for optimal communication, decision-making, and collaborative and integrated working. A realist review approach will be used to synthesise the evidence to make sense of the complexities inherent in the working relationships between GP and CP. Our review will follow Pawson’s five iterative stages: (1) finding existing theories; (2) searching for evidence (our main searches were conducted in April 2022); (3) article selection; (4) data extraction and (5) synthesising evidence and drawing conclusions. We will synthesise evidence from grey literature, qualitative, quantitative and mixed-methods research. The research team will work closely with key stakeholders and include patient and public involvement and engagement throughout the review process to refine the focus of the review and the programme theory. Collectively, our refined programme theory will explain how collaborative and integrated working between GP and CP works (or not), for whom, how and under which circumstances. Ethics and dissemination Formal ethical approval is not required for this review as it draws on secondary data from published articles and grey literature. Findings will be widely disseminated through: publication in peer-reviewed journals, seminars, international conference presentations, patients’ association channels, social media, symposia and user-friendly summaries.