Our purpose is to develop and propose a conceptual framework based on respect, relationship, representation, relevance, responsibility, and reciprocity (the Six Rs), to be applied in studies using Indigenous research methodologies (IRMs). This conceptual framework builds upon the extensive work of numerous Indigenous scholars who brought this conversation into the literature and research enterprise. Our goal is to synthesize the Six Rs, describe how they complement and inform one another, and explain our process for their implementation and interpretation as a framework to develop and answer research questions. The Six Rs provide a representative research framework and can be a powerful guideline.