As clinical research moves toward real-world data capture with increased data sharing, there is a growing need for patient-centered technologies that ensure data authenticity and promote researcher and patient access. Blockchain is one of an emerging set of distributed ledger technologies with the potential to offer both research data transparency and trust, while offering robust security measures. As blockchain-based systems are being developed for clinical research applications, these systems may be required to follow state and federal research regulations, such as ethical protections for human participants and data privacy. Blockchain developers and research organizations alike are struggling to identify and interpret these regulatory requirements. Further, regulatory agencies and policymakers have not yet provided blockchain stakeholders with clear guidelines to achieve compliance. This article provides an introduction to the clinical research and health information privacy regulations in the United States as well as data design standards and electronic signature laws. We also offer recommendations for blockchain developers, researchers, and research organizations for achieving compliant blockchain solutions in clinical research.