BACKGROUND: Given the complex determinants of non-communicable diseases (NCDs), and the dynamic policy landscape, researchers and policymakers are exploring the use of systems thinking and complexity science (STCS) in developing effective policies. The aim of this review is to systematically identify and analyse existing applications of STCS-informed methods in NCD prevention policy. METHODS: Systematic scoping review: We searched academic databases (Medline, Scopus, Web of Science, EMBASE) for all publications indexed by 13 October 2020, screening titles, abstracts and full texts and extracting data according to published guidelines. We summarised key data from each study, mapping applications of methods informed by STCS to policy process domains. We conducted a thematic analysis to identify advantages, limitations, barriers and facilitators to using STCS. RESULTS: 4681 papers were screened and 112 papers were included in this review. The most common policy areas were tobacco control, obesity prevention and physical activity promotion. Methods applied included system dynamics modelling, agent-based modelling and concept mapping. Advantages included supporting evidence-informed decision-making; modelling complex systems and addressing multi-sectoral problems. Limitations included the abstraction of reality by STCS methods, despite aims of encompassing greater complexity. Challenges included resource-intensiveness; lack of stakeholder trust in models; and results that were too complex to be comprehensible to stakeholders. Ensuring stakeholder ownership and presenting findings in a user-friendly way facilitated STCS use. CONCLUSION: This review maps the proliferating applications of STCS methods in NCD prevention policy. STCS methods have the potential to generate tailored and dynamic evidence, adding robustness to evidence-informed policymaking, but must be accessible to policy stakeholders and have strong stakeholder ownership to build consensus and change stakeholder perspectives. Evaluations of whether, and under what circumstances, STCS methods lead to more effective policies compared to conventional methods are lacking, and would enable more targeted and constructive use of these methods.