The design community, along with other research communities, is called upon to tackle the complex global challenges framed in the United Nation’s 17 Sustainable Development Goals (SDGs). However, these require design research to be conducted in Global South contexts, in low- and middle-income countries (LMICs), where to date design research has been limited or non-existent. This is reflected in the funding opportunities available for international research, particularly those focused on the Global South, which employ the SDGs as a framework for research, for example, the Global Challenges Research Fund in the UK and the Newton and British Academy Funds. Conducting design research in the Global South, therefore, introduces a new context where cultural, social, religious and administrative practices often pose challenges but can create new opportunities for researchers from across the globe. Applying design research that addresses SDGs in Global South contexts requires cross-disciplinary collaboration, navigating cultures, diversity, ethics and the habits of different design communities. This in turn requires new processes or their adaptation to deal with challenges related to multiple voices, participation and power distribution, the role of communities and public organisations and the building of international Global North-Global South partnerships in and for design research. In this chapter we present the challenges and lessons learned from previous international design-led/design-related research projects and studies from the literature and an international workshop on the subject which took place in September 2019 in Manchester, UK.