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Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial diversity in vertebrate models presents a significant challenge for investigating host–microbiome interactions. The model organism <i>Caenorhabditis elegans</i> has many advantages for delineating the effects of host genetics on microbial composition. In the wild, the <i>C. elegans</i> gut contains various microbial species, while in the laboratory it is usually a host for a single bacterial species. There is a potential host–microbe interaction between microbial metabolites, drugs, and <i>C. elegans</i> phenotypes. This mini-review aims to summarize the current understanding regarding the microbiome in <i>C. elegans</i>. Examples using <i>C. elegans</i> to study host–microbe–metabolite interactions are discussed.