AbstractTechnologies capable of noninvasively sampling different locations in the gut upstream of the colon will enable new insights into the role of organ‐specific microbiomes on human health. Herein, an ingestible pill for the sampling of gut lumen based on one of the earliest hydraulic machines known as an Archimedes screw is reported. The design contains twisted wires as Archimedes screw driven by a motor, wirelessly activated using a magnet. The sampling performance of the screw‐pump pill is characterized using realistic in vitro models and validated in vitro using E. coli expressing different fluorescent proteins. The use of the Archimedes screw enables the pill to sample the dense GI environment. The pill is also tested ex vivo in the pig intestine and in vivo in pigs. Herein, the results show that the bacterial populations recovered from the pill's chamber closely resemble the targeted bacterial population of the microenvironment to which the pill is exposed. Such ingestible devices have the potential to revolutionize the understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.