Clinical research is complex, and research-related terms can be challenging to understand. Clear, supportive communication with patients, potential study participants, and their caregivers must be prioritized by healthcare providers as well as investigators and their research teams. In clinical research, health literacy best practices support the ethical tenets of respect, justice, and beneficence. Plain language advances the understanding of informed consent documents, as well as comprehension of educational information, recruitment materials, study instructions, and study results summaries, among others. Further, a more collaborative research partnership is fostered when study participants are given understandable materials, while a lack of understanding can delay accrual and decrease adherence. We launched a pilot initiative to develop a consensus-driven, plain language clinical research glossary to promote clarity, consistency, and transparency across clinical research stakeholder groups. The resulting resource, described herein, is intended to be used widely to support a greater understanding of clinical research and empower study participants. Considerations for expansion are also discussed.