Background <p>Rare diseases (i.e., incidence of &lt;1/2000) are individually uncommon, but collectively these 10,000 conditions affect an estimated 473 million people globally, and approximately 70% of rare diseases manifest in childhood. Despite this global impact, 90% of rare diseases lack effective treatment. Treatments for rare diseases are often identified through clinical trials. Identifying parents’ knowledge needs and preferences regarding pediatric rare disease clinical trials is an important aspect of empowering parents, improving clinical research practices, and potentially improving recruitment to these vital trials. The aim of the scoping review is to determine the extent, range, and characteristics of the evidence on the knowledge needs and preferences of parents regarding pediatric rare disease clinical trials.</p> Methods <p>A scoping review will be conducted to identify sources of literature on the topic. A systematic search strategy co-developed with a research librarian will be conducted in six databases (Medline, EMBASE, CINAHL, Scopus, Web of Science, and PsycINFO). Gray literature will be searched via Google, Perplexity AI, the ProQuest Dissertations &amp; Theses Global database, and relevant rare disease organizational websites. Abstract and full-text screening will be conducted by two reviewers independently. Studies in English will be included regardless of study design, date of publication, or location of study/publication. Study quality will be appraised using the Mixed Methods Appraisal Tool. Data will be extracted including study characteristics, population, phenomena under investigation, and knowledge needs and preferences identified. Analysis will involve a descriptive numerical summary and qualitative content analysis. Findings will be presented in evidence tables, and patterns, themes, and gaps across the data will be reported using a narrative approach.</p> Discussion <p>This review will provide an overview of the existing literature regarding parents’ knowledge needs and preferences about pediatric rare disease clinical trials. The findings of this review will inform future research and the development of knowledge translation resources for parents of children with rare diseases.</p> Systematic review registration <p>This protocol has been registered in Open Science Framework (registration: <a href="https://doi.org/10.17605/OSF.IO/QXR8G">https://doi.org/10.17605/OSF.IO/QXR8G</a>).</p>