The world is currently dealing with one of the most severe health, economic and social crises in recent memory, through coronavirus disease 2019 (COVID-19). Scholars are converging on the perspective that traditional means of addressing these crises have served their time. On the additional backdrop of a global political landscape in transition, realising a post-pandemic recovery will require new modes of international collaboration with scientific knowledge and expertise figuring more prominently. A smart approach to science diplomacy—to global resilience through knowledge-based cooperation—does not prescribe the content, but rather focuses on the process of science-based international exchange. The new Protocol for Science Diplomacy presented in this policy brief inspires the alignment of shared, cosmopolitan interests and their application to cross-border societal challenges. It comprises a set of 12 procedural and infrastructural principles with which actors can create a space for constructive and productive science diplomacy interactions. These principles are: sensitivity; inclusiveness; transparency; deliberation; reciprocity; complementarity & manoeuvrability; legitimacy; alignment; evaluation; capacities; capabilities; trust. Our Protocol for Science Diplomacy identifies ground rules for international scientific and policy collaboration that enable us, inter alia, to make meaningful steps towards tackling the United Nations’ (UN) Sustainable Development Goals (SDGs) by their 2030 deadline. As such, it offers a roadmap for science diplomacy in the next decade and beyond.