Self-directed learning and design thinking were found to be promising pedagogies for supporting education and thus supporting sustainable development goals. While some researchers have posited that self-directed learning may support design thinking, empirical research examining the relationship between these two essential skills is lacking because their shared conceptual structure has not been articulated in detail, and because they have remained siloed in design practice. This study examines pre-service teachers’ self-regulation in relation to design thinking skills to advance a theoretical understanding of design science and to overcome challenges teachers face in adopting and implementing design thinking. For this study, 158 pre-service teachers were recruited. On the first level, the empirical data collected were subjected to structural equation modelling to find and confirm significant metacognitive perspectives in design thinking, while on the second level, an in-depth analysis was conducted to find moderating effects of pre-service teachers’ metacognitive experiences and teacher education in design thinking. We argue that awareness and interpersonal skills are crucial in creative design activity, and that embracing risk, tolerance to uncertainty, and underdeveloped supervising skills might be critical elements for advancing design thinking behaviour. The findings of this study have implications for effective science and technology teaching and the learning of design thinking in teacher education, and for educators and commercial course designers to adjust the implementation of design thinking.