Background and Objectives: Design thinking is a participatory problem-solving method with a human-centered approach that enhances innovation by enhancing learners' creative thinking abilities. Although design thinking has become an integral part of design and engineering as well as business, it can have a positive impact on the 21st century education in other fields, too. Using design thinking in educational settings, students read, think, and reason logically and can solve complex problems. However, there are several definitions of design thinking, as many authors have stated that there is no fixed universal definition of design thinking. Therefore, it seems necessary to try to understand and demystify design thinking. In this regard, the purpose of this study researchis to analyze the concept of design thinking and study the models of design thinking and definitions of the 21st century skills as well as the role of design thinking on the 21st century skills by systematic collecting, evaluating and reviewing the related articles on this topic. Methods: In this study, searches were performed in the databases of Eric, ScienceDirect, Taylor and Francis, Springer, and Google Scholar, and all articles indexed in their databases from 2000 to 2020 were collected in English. After searching the databases, the relevant articles were selected and evaluated according to the CASP evaluation criteria. After reading the abstracts and the initial review and removal of irrelevant articles, the full version of 83 articles was prepared and reviewed. Then, among the available articles, the relevant ones were selected and evaluated for detailed evaluation based on CASP evaluation criteria. Also, in the manual search that was done through the sources of articles, according to the nature of design thinking, 3 reference sites were added to present the model and 3 books and 2 websites were added for the skills of the 21st century. Finally, 54 articles, books and websites were selected for detailed study. Findings: According to the obtained/aforementioned studies, they were categorized in four groups: 1-Articles that have explained the skills of the 21st century. 2-Articles that have offered a new definition of design thinking. 3-Articles that have presented new models of design thinking. 4-Articles that have used the models in implementing the design and improving the skills of the 21st century. Given the results, despite the similarities and connections that can be identified in the context of 21st century skills, different terms and definitions are often used to describe a skill or a set of skills that cause ambiguity and confusion. In this regard, the skills that are mentioned in all frameworks are as follows: cooperation and communication,ICT literacy,social skills,creativity,critical thinking,problem solving, production of quality products and productivity. The results of the studies also showed that the implementation of design thinking leads to strengthening problem-solving skills, innovation and creativity, and the skill of using integrated thinking. Continuing the implementation of design thinking along with empathy, cooperation, teamwork leads to selfconfidence and value of the learner. Conclusion: According to the research results, in general, it can be said that today's society needs to educate a generation equipped with the 21st century skills to advance the high goals of the society, so paying attention to creating the necessary conditions for the implementation of design thinking plays a unique role in raising a productive generation.