Abstract Based on International Relations (IRs) grounding theories, this article outlines a realist-constructivist perspective in science diplomacy when assessing a nation-state’s foreign policy decision-making and behaviour. The proposed theoretical framing helps us evaluate existing practices of science diplomacy within the larger context of IRs and allows us to better understand the increasing role of science diplomacy and its potency in the foreign policy of emerging and developing countries. The proposed exploratory research methodology outlines the contours of a science diplomacy reading grid breaking it down into the categories of objectives, strategic drivers, and tools. The data collection and semi-structured interviews with high-ranking practitioners and experts allowed us to assess the meaning of science diplomacy as understood and implemented by Global South countries and to distinguish science diplomacy practices as oriented towards the satisfaction of domestic needs and international positioning.