The work presented is a comprehensive review of the role of the human microbiota in the context of the COVID-19 pandemic. A diverse microbial community heavily colonizes the human body called the microbiota, with the gut microbiota being the most diverse. The composition of the microbiota varies in different parts of the body and changes with age, diet, and other environmental factors. Emerging evidence suggests that the gut microbiota plays a critical role in modulating the host immune response and may influence the severity of COVID-19. Patients with COVID-19 have significant alterations in their gut and respiratory microbiota, characterized by a depletion of beneficial commensal bacteria and an enrichment of opportunistic pathogens. These changes in microbiota composition are associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. In addition, changes in the gut microbiota can affect lung and brain function, influencing the severity of COVID-19 cases and neurological symptoms, as well as long-term neurological complications associated with the disease. Due to the importance of the microbiota in COVID-19, several therapeutic approaches targeting the microbiota have been proposed to improve outcomes in this disease, including fecal microbiota transplantation, probiotic and prebiotic supplementation, postbiotic or microbiota-derived metabolite supplementation, dietary interventions, and lifestyle strategies. Overall, the review highlights the critical role of the human microbiota in the pathogenesis and progression of COVID-19 and the potential of microbiota-targeted interventions to improve patient outcomes. HIGHLIGHTS COVID-19 causes gut microbiota dysbiosis, associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. Gut microbiota dysbiosis due to COVID-19 affects lung and brain function, which is associated with the severity of COVID-19 cases. Gut microbiota is crucial in COVID-19, so several strategies have been developed to regulate it in COVID-19 cases, such as fecal microbiota transplantation, probiotics, and prebiotics, among others. GRAPHICAL ABSTRACT