The proceedings of the National Science Foundation supported WIS2DOM workshop state that sustainability scientists must respect the “protocols” of practitioners of Indigenous sciences if the practitioners of the two knowledge systems are to learn from each other. Indigenous persons at the workshop described protocols as referring to attitudes about how to approach the world that are inseparable from how people approach scientific inquiry; they used the terms caretaking and stewardship to characterize protocols in their Indigenous communities and nations. Yet sustainability scientists may be rather mystified by the idea of protocols as a necessary dimension of scientific inquiry. Moreover, the terms stewardship and caretaking are seldom used in sustainability science. In this case report, the authors seek to elaborate on some possible meanings of protocols for sustainability scientists who may be unaccustomed to talking about stewardship and caretaking in relation to scientific inquiry. To do so, the authors describe cases of Indigenous protocols in action in relation to scientific inquiry in two Indigenous-led sustainability initiatives in the Great Lakes/Midwest North American region. We claim that each case expresses concepts of stewardship and caretaking to describe protocols in which humans approach the world with the attitude of respectful partners in genealogical relationships of interconnected humans, non-human beings, entities and collectives who have reciprocal responsibilities to one another. We conclude with a discussion of the implications of Indigenous protocols for future dialog between practitioners of sustainability and Indigenous sciences.