Introduction: Diabetes and related metabolic disorders such as obesity and cardiovascular diseases (CVD) are a growing global issue. Equipping individuals with the necessary ‘knowledge, skills and confidence to self-manage their health’ (i.e. patient activation [PAct]) may lead to improvements in health outcomes. It is unclear whether existing evidence allows us to assume a causal relationship. We aim to synthesise and critically appraise evidence on the relationship between PAct and self-management behaviours and clinical outcomes of people living with diabetes and related metabolic disorders. Methods and analysis: The protocol is based on guidance on Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will search Medline, Embase, CENTRAL, PsycInfo, Web of Science, and CINAHL using search terms related to patient activation, diabetes, prediabetes, obesity, and cardiovascular disease. Any quantitative study design is eligible provided studies assess the association between PAct and clinical outcomes and/or self-management behaviours of diabetes and related metabolic disorders. Outcomes include behavioural (e.g. diet) and clinical (e.g. blood pressure) outcomes. Two reviewers will independently screen titles/abstracts and full texts and assess risk of bias using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). One reviewer will extract data, with independent checking by a second reviewer. We will critically assess the level of evidence available for assuming a causal association between PAct and outcomes. Data permitting, we will use the Hunter-Schmidt random-effects method to meta-analyse correlations across studies. Ethics and dissemination: Ethical approval is not required. The review will be disseminated in the form of a peer-reviewed journal article, at conferences and other presentations. The findings of the review will be of interest to clinical commissioning groups, policy makers and intervention deliverers/developers. Registration: Prospero registration number: CRD42021230727