During HIV infection, massive destruction of CD4+ T cells ensues, preferentially depleting the Th17 subset at the gut-associated lymphoid tissue (GALT), leading to a loss of mucosal integrity and an increase in cell permeability. This process favors microbial translocation between the intestinal lumen and the circulatory system, contributing to persistent immune activation and chronic inflammation characteristic of HIV infection. Thus, the gut microbiota plays an integral role in maintaining the structure and function of the mucosal barrier, a critical factor for immune homeostasis. However, in the context of HIV infection, changes in the gut microbiota have been reported and have been linked to disease progression. Here, we review evidence for the role of the gut microbiota in intestinal homeostasis, its contribution to HIV pathogenesis, as well as its use in the development of therapeutic strategies.