This paper provides insights into the practice of design-based interventions in transdisciplinary research and demonstrates how design prototyping can be made fruitful in processes of transformation and collaborative knowledge production. It shows how heterogeneous perspectives and stocks of knowledge can be related to each other and moments of integration generated by working with conceptual designs. Due to their open character, design methods are discussed as particularly promising when dealing with a high degree of complexity, uncertainties, and unknowns. After a characterization of design research and prototyping, common strategies of design research and transdisciplinary research for addressing heterogeneity and unknowns will be explored. This serves to frame the transfer of design practices to support integration processes in transdisciplinary teams. Using an example from a transdisciplinary case study in Transylvania, the implementation of design prototyping will be demonstrated and initial findings presented. Different integration dimensions from transdisciplinary sustainability research serve as a basis for investigating the epistemic, social-organizational, and communicative integration performance of design prototyping. For transdisciplinary research, design practices expand the methodical canon for working in heterogeneous teams and tackling uncertainty and unknowns in openness.