ObjectivesThe epidemiological transition from infectious to chronic diseases leads to novel challenges in African health systems. The prevalence of diabetes mellitus (DM) is increasing dramatically. Undiagnosed and undertreated DM leads to numerous complications including end-organ damage and death. Our objectives were to collect the best locally generated evidence on DM interventions, identify knowledge gaps and determine underexplored research areas.DesignA systematic review and meta-analysis of randomised controlled trials.Participants and settingAfrican patients in primary, secondary and tertiary prevention, diagnosis and treatment DM type 1 (DM1), type 2 (DM2) and gestational DM (GDM).OutcomeAll-cause mortality, glycaemic control, complications, quality of life, hospital admission, treatment adherence and costs.Data sourcesArticles published in MEDLINE Ovid, CENTRAL, CINAHL, African Journals Online and African Index Medicus and the International Clinical Trials Registry Platform in English language without time restrictions. The systematic search was last updated in October 2020.ResultsOut of 3736 identified publications, we included 60 eligible studies conducted in 15 countries, 75% were conducted in urban healthcare settings, including 10 112 participants. We included 8 studies on DM1, 6 on GDM, 2 on pre-DM, 37 on mainly DM2 including 7 on DM-related complications. The design of the studied intervention was heterogeneous with a focus on educational strategies. The other studies investigated the efficacy of nutritional strategies including food supplementations, pharmacological strategies and strategies to enhance physical activity. Seven studies included interventions on DM-related complications.ConclusionsResearch activities increased in recent years, but available evidence is still not representative for all African countries. There is a big lack of evidence in primary healthcare and rural settings, implementation research, pharmacological interventions, especially in poorer countries. Nevertheless, the identified studies offer a variety of effective interventions that can inform medical care and future research.PROSPERO registration numberCRD42019122785.