Introduction: Alteration in humans’ gut microbiota was reported in patients infected with SARS-CoV-2. The gut and upper respiratory tract microbiota harbor a dynamic and complex population of microorganisms and have strong interaction with host immune system homeostasis. However, our knowledge about microbiota and its association with SARS-CoV-2 is still limited. We aimed to systematically review the effects of gut microbiota on the COVID-19 infection and its severity and the impact that SARS-CoV-2 could have on the gut microbiota.Methods: We searched the keywords in the online databases of Web of Science, Scopus, PubMed, and Cochrane on December 31st, 2021. After duplicate removal, we performed the screening process in two stages; title/abstract and then full-text screening. The data of the eligible studies were extracted into a pre-designed word table. This study adhered to the PRISMA checklist.Results: Sixty-three publications were included in this review. It appeared that COVID-19 infection could affect the microbiome in patients, particularly in moderate and severe cases. The severity of COVID-19 disease may also be influenced by the microbiota's composition through immunological responses or some other unknown mechanisms.Conclusion: Our study showed that there was a significant change in the composition of the upper respiratory tract and gut microbiome in patients with COVID-19 compared to healthy individuals. These apparent changes suggested gut and upper respiratory tract microbiota as a possible indicator for diagnosis and strategy for the treatment of COVID-19.