Randomized clinical trials (RCT) involve labor-intensive, highly regulated, and controlled processes intended to transform scientific concepts into clinical outcomes. To be effective and targeted, it is imperative they include those populations who would most benefit from those outcomes. Alzheimer's disease (AD) is most detrimental to the aging population, and its clinical manifestation is influenced by socio-economic factors such as poverty, poor education, stress, and chronic co-morbidities. Indigenous populations in the United States and Canada are among the minority populations most influenced by poor socio-economic conditions and are prone to the ravages of AD, with Indigenous women carrying the added burden of exposure to violence, caregiving stresses, and increased risk by virtue of their sex. Race- and sex-based disparities in RCT enrollment has occurred for decades, with Indigenous men and women very poorly represented. In this review, we examined literature from the last twenty years that reinforce these disparities and provide some concrete suggestions and guidelines to increase the enrollment numbers in AD RCT among this vulnerable and poorly represented population.