The prevalence of periodontal disease varies considerably between Indigenous and general populations. The aim of this systematic review was to assess the global prevalence of periodontal disease among Indigenous populations in comparison with non-Indigenous populations. A systematic electronic search of databases and grey literature sources was conducted of all records through to February 2021. Study selection criteria included original data that reported the prevalence of periodontal diseases among an Indigenous population and compared with a non-Indigenous population, without any restriction on age, sex, language or geographical location. Critical appraisal was conducted with the Joanna Briggs Institute (JBI) tool for prevalence studies. A random-effects model using standardised mean difference (SMD) as the effect measure was used to estimate the pooled prevalence of periodontitis. Subgroup analysis of study location and publication source was also performed. Publication bias was assessed using Egger's test, and funnel plots were used for visualisation. A total of 19 articles were included for descriptive and meta-analysis. The overall prevalence of periodontitis was 35% (95% CI: 0.18, 0.52) higher among the Indigenous population than the non-Indigenous population. The pooled prevalence of periodontitis was consistently higher among the Indigenous populations when stratified according to periodontitis definition employed, study location and publication source. Indigenous populations have a higher prevalence of periodontitis than non-Indigenous populations. To decrease oral health inequities, more emphasis should be given to oral health promotion and specific culturally safe interventions working in partnership with Indigenous populations.