<p>Recently, research on blockchain applications in the healthcare research domain has attracted increasing attention due to its strong potential. However, the existing literature reveals limited studies on defining use cases of blockchain in clinical research, categorizing and comparing available studies. Therefore, this study aims to explore the significant potential and use cases of blockchain in clinical research through a comprehensive systematic literature review (SLR). To thoroughly investigate all aspects of the subject, we analyzed primary studies based on research questions (RQs) and developed a unified <i>conceptual model</i> using <i>step-based model creation</i>. Studies from 2015 to 2023 were reviewed, and 34 primary studies were comprehensively analyzed by using the PICO template. In our findings, <i>privacy</i> emerged as the most frequently cited requirement in clinical research. The most mentioned use cases for blockchain are <i>ensuring data immutability</i> and <i>security</i>. A significant issue identified beyond the common blockchain limitations of capacity and scalability is the <i>lack of standards for compliance with legal frameworks</i> like GDPR and HIPAA. After all these efforts, we developed a conceptual model, which, to our best knowledge, is the first in the literature to support software developers and clinical researchers in developing and using blockchain-based research platforms efficiently.</p> Graphical abstract <p></p>