The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients. Additionally, the respiratory and GI tracts express high level of transmembrane protease serine 2 (TMPRSS2) and angiotensin-converting enzyme-2 (ACE2), making them primary sites for human microbiota and targets for SARS-CoV-2 infection. A growing body of research indicates that individuals with COVID-19 and post-acute COVID-19 syndrome (PACS) exhibit considerable alterations in their microbiome. In various human disorders, including diabetes, obesity, cancer, ulcerative colitis, Crohn's disease, and several viral infections, the microbiota play a significant immunomodulatory role. In this review, we investigate the potential therapeutic implications of the interactions between host microbiota and COVID-19. Microbiota-derived metabolites and components serve as primary mediators of microbiotahost interactions, influencing host immunity. We discuss the various mechanisms through which these metabolites or components produced by the microbiota impact the host's immune response to SARS-CoV-2 infection. Additionally, we address confounding factors in microbiome studies. Finally, we examine and discuss about a range of potential microbiota-based prophylactic measures and treatments for COVID-19 and PACS, as well as their effects on clinical outcomes and disease severity.