The intestinal microbiota of humans supports essential functions. Alteration of the microbiota, known as dysbiosis, is associated with aging and a wide spectrum of disorders, including cancer. The complexity and diversity of the human microbiota poses a challenge for investigating the molecular mechanism of the microbiota in physiology and pathology. Caenorhabditis elegans, a model organism, possesses genetic tractability and certain similarities to the microbiota in humans, and has been employed for understanding how the microbiota may impact aging and the development of certain cancers. The development of culture independent technologies could shed light on the function of the microbiota and the microbiome. This mini-review aims to update current understanding regarding the human microbiota during aging and immune development. Examples of using C. elegans as an ideal model in studying the intricate host-microbe-drug interaction, particularly in metformin-derived anti-cancer and anti-aging effects, are discussed.