BACKGROUND: Novel coronavirus pneumonia (COVID-19) has become a worldwide epidemic, causing huge loss of life and property. Because of its unique pathological mechanism, diabetes affects the prognosis of patients with COVID-19 in many aspects. At present, there are many controversies about whether angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) should be used in the treatment of patients with diabetes mellitus and COVID-19 comorbidities. There is an urgent need to provide evidence for the use of ACEI/ARB through high-quality systematic evaluation and meta-analysis. METHODS: We will search electronic databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and Wanfang database using keywords related to COVID-19, diabetes mellitus, ACEI/ARB drugs, and randomized controlled trials . We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies, extract data, and evaluate risk of bias. Data analysis will be conducted using the Review Manager software version 5.3.5 and stata 14.0 software for Mac. Statistical heterogeneity will be assessed using a standard chi-square test with a significance level of P < .10. Biases associated with study will be investigated using funnel plots. RESULTS: This study will provide a high-quality synthesis of efficacy and safety of ACEI/ARB drugs in patients with COVID-19 combined with diabetes mellitus, providing evidence for clinical treatment of diabetes mellitus combined with COVID-19. And the results will be published at a peer-reviewed journal. CONCLUSION: Our study will draw conclusions on the efficacy and safety of ACEI / ARB drugs in patients with diabetes mellitus complicated with covid-19, so as to provide theoretical guidance for clinical practice of diabetes mellitus with covid-19. INPLASY REGISTRATION NUMBER: INPLASY 202060111.