Glycans cover the surfaces of all cells, where they are poised to mediate a two-way discourse between bacteria and host cells. In some instances, glycan-mediated interactions foster a symbiotic state, and in others, they tip the balance toward disease. Chemical biology approaches have begun to reveal the roles of glycans in host-bacteria interactions and provide novel pathways to modulate these interactions. Here, we highlight recent advances in the development and application of chemical biology tools to delineate the roles of glycans in bacterial adhesion, bacterial evasion of the host immune system, host recognition of bacterial cells, and endogenous mechanisms to maintain symbiosis. Further, we present glycan-based strategies to disrupt host-pathogen interactions and to promote the growth of beneficial bacteria.