Introduction: The provision of ancillary care is increasingly becoming recognised as an ethical requirement in healthcare-related research across the globe. This does, however, raise complex ethical concerns when research is conducted in resource-constrained settings where participants may have additional healthcare needs that fall outside the scope of the research and are not provided for by the local healthcare system. Despite growing calls for the provision of ancillary care to study participants during medical research, there remains a noticeable gap in ethics guidelines for medical researchers in resource-constrained settings. I aim to address this evidence gap by examining the existing ethical and policy guidance, current practices, research stakeholders' perspectives on the provision of ancillary care in medical research, and the ethical and social implications of this in the global south. Methods: First, I conducted a systematic review and meta-synthesis of research published between 2004 and 2020 to understand the practices relating to ancillary care during medical research in East and Southern Africa. A database search was conducted, and all the papers included (24 out of 4,710) were appraised for methodological quality and assessed to see if they reported on ancillary care provision to study participants. Next, I undertook a chronological discourse analysis of research guidance documents. For this, 34 documents outlining international ethical guidelines and policy were reviewed to explore the evolution of language referring to ancillary care and the way it has been used in different documents. Finally, I gathered primary data from research stakeholders in Malawi on their experiences of and views on ancillary care. I conducted a qualitative methods study between September 2021 and June 2022 in Malawi, gathering data, through in-depth interviews, on the experiences of 45 research stakeholders (including researchers, research ethics committee members, health officials, researcher funders and study participants) and their perspectives of ancillary care. I also explored research stakeholders’ views on the impact of ancillary care in medical research conducted in resource-constrained settings. Results: The systematic review and meta-synthesis showed that approaches to the provision of ancillary care in health-related research are not standardised, and ethics guidance is not consistent. In the discourse analysis, I found varied interpretations of ancillary care language, leading to diverse applications in practice due to the absence of explicit definitions in international ethics guidelines. In the qualitative in-depth interview study in Malawi, all stakeholders perceived the significant role of ancillary care in promoting participants' well-being and viewed it as a way for researchers to demonstrate reciprocity. Still, they were concerned about the absence of ethical guidance to support it. There was a suggestion that consideration of ancillary care could be possible on a case-by-case basis but that most of the support from research projects should be directed towards strengthening the public health system, emphasising public good above personal benefit. Funding for the research was also recognised as a limiting factor for ancillary care, owing to the potential conflict between meeting study demands and treating participants’ additional health conditions. Conclusion: My findings provide evidence that the practice of ancillary care provision in health-related research in resource-constrained settings is limited by the absence of guidelines for researchers regarding what ancillary care to provide and how to provide it. The study identifies key principles to consider when addressing ancillary care, emphasizing the urgent need to establish formal ethical frameworks that safeguard the well-being of research participants. Through the application of constructivist and interpretivist epistemological approaches, this research promotes culturally sensitive and contextually grounded ethical practices, enhancing research integrity in the global south. The implications of this study call for increased awareness and collaboration among researchers, institutions, and funders to ensure equitable and ethically responsible research conduct, ultimately improving ancillary care practices and participant welfare in RCS. Furthermore, the study provides insights that could inform future strategies for engaging international and local research ethics and regulatory bodies in developing specific guidelines for the provision of ancillary care in these settings. Future research might investigate the question of whether ancillary care should prioritise individual participants over public benefit.