Clinical trials for rare diseases face significant challenges, including scarce patient samples, high heterogeneity, and considerable difficulties in research and development. Patient participatory design, guided by the principles of "how", "for whom" and "with whom", facilitates the transition of patients from passive "subjects" to active "research participants," with the aim of better addressing patient needs, optimizing trial design, and enhancing research quality. Adopting the perspective of design ethics, this article systematically reviews the ethical guidelines and frameworks for patient involvement in clinical trial design proposed by institutions such as the UK National Institute for Health and Care Research and the US Patient−Centered Outcomes Research Institute, offering a comparative analysis of their core principles and content. On this basis, the article critically examines key ethical issues faced by patients with rare diseases during the design process, including equitable participation, the establishment of partnership, privacy protection, and the identification of core needs. It also explores the tensions encountered when applying universal guidelines to the context of rare diseases. The study proposes the establishment of values centered on equitable collaboration, ensuring transparent and accessible information exchange, constructing a lifecycle engagement process, and carefully addressing the conflict between the vulnerability of patient populations and the inherent uncertainties of research. This article aims to provide a theoretical foundation and practical reference for refining the ethical governance system in the design phase of rare disease clinical trials and for advancing the paradigm shift towards "patient−centric" research.