BACKGROUND: Coronavirus disease (COVID-19) sparked global concern for its outbreak and pandemic. It caused severe respiratory tract infections and a significant proportion of patients with gastrointestinal symptoms. Several studies have investigated the intestinal flora of COVID-19. However, so far there has been no evidence demonstrating the evidence on the association of COVID-19 with intestinal flora through meta-analysis. A systematic and comprehensive understanding of their relationship is essential to provide public health prevention or treatment strategy. METHODS AND ANALYSIS: This systematic review and meta-analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies (cohort studies, case-control, and cross-sectional studies) and clinical trials will be eligible. Studies eligible for inclusion must contain participants with COVID-19. Systematic searches will be conducted in PubMed, EMBASE, Cochrane Library, Ovid, EBSCO, World Health Organization COVID-19 database, China National Knowledge Internet, WanFang Data, Chinese Scientific and Technological Journal Database, and Chinese Biomedical Databases. A pre-designed search strategy of medical subject headings and free text terms for COVID-19 and intestinal flora will be used. Two reviewers will independently screen the titles and abstracts, followed by full-text screening. Discrepancies will be resolved by consensus with a third reviewer. The reviewers will then extract data from each eligible article based on PECOS (Population, Exposure, Comparator, Outcomes, and Study design). The risk of bias and quality of included studies will be assessed using an appropriate tool. A random-effects meta-analysis will be considered where there are sufficiently homogeneous studies; otherwise, a narrative synthesis will be conducted. Heterogeneity among studies will be assessed using I statistics. If substantial heterogeneity detected, subgroup analyses and meta-regression will be conducted to look for the potential causes. ETHICS AND DISSEMINATION: Ethical approval is not required as we will use data from published articles. Findings will be published in a peer-reviewed journal.PROSPERO registration number: CRD42020191640.