Host-associated microbial communities are essential for organismal and environmental homeostasis, and their disruption is linked to disorders ranging from immune and inflammatory disease in mammals to impaired growth and reduced pathogen resistance in plants. Despite their importance, current therapeutic and agricultural strategies remain poorly equipped to intervene in the complexity and variability of microbiomes. Our goal is to harness the extraordinary chemical diversity of dietary and medicinal plants to uncover how bioactive metabolites mechanistically shape microbial communities, and how these interactions, in turn, influence host and environmental health and disease. Our research group integrates techniques in plant synthetic biology, high-throughput microbial screening, and chemical genomics to generate mechanistic, systems-level frameworks for how botanicals shape diverse microbe–host symbioses, enabling new strategies for precision microbiome editing.