Indigenous Peoples in Canada are comprised of First Nations, Inuit and Métis and are the youngest and fastest growing population in the country. However, there is limited knowledge of how they are affected by multiple sclerosis (MS), the most common nontraumatic neurological disease of young adults, with Canada having one of the highest prevalences in the world. In this narrative review, we outline the limited studies conducted with Indigenous Peoples living with MS in Canada and the gaps in the literature. From the limited data we have, the prevalence of MS in Indigenous Peoples is lower, but the disease appears to be more aggressive. Given the dearth of Canadian data, we explore the worldwide MS studies of Indigenous populations. Lastly, we explore ways in which we can improve our understanding of MS among Indigenous Peoples in Canada, which entails building trust and meaningful relationships with these communities and acknowledging past and ongoing injustices. Furthermore, healthcare professionals conducting research with Indigenous Peoples should undergo training in cultural safety and data sovereignty, including principles of ownership, control, access and possession to have greater engagement with Indigenous communities to conduct more relevant research. With joint efforts between healthcare professionals and Indigenous communities, the scientific research community can be positioned to conduct better, more appropriate and desperately needed research, ultimately with improvements in the delivery of care to Indigenous Peoples living with MS in Canada.