The gut microbiota is essential for good health. It has also been demonstrated that the gut microbiota can regulate immune responses against respiratory tract infections. Since the outbreak of the COVID-19 pandemic, accumulating evidence suggests that there is a link between the severity of COVID-19 and the alteration of one’s gut microbiota. The composition of gut microbiota can be profoundly affected by COVID-19 and vice versa. Here, we summarize the observations of the mutual impact between SARS-CoV-2 infection and gut microbiota composition. We discuss the consequences and mechanisms of the bi-directional interaction. Moreover, we also discuss the immune cross-reactivity between SARS-CoV-2 and commensal bacteria, which represents a previously overlooked connection between COVID-19 and commensal gut bacteria. Finally, we summarize the progress in managing COVID-19 by utilizing microbial interventions.