Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine. Graphical abstract The gut microbiota may influence the bioavailability of oral drugs by the microbial enzyme activity, affecting the drug transport or changing the gastrointestinal properties. This may provide us some advice on preventing the possible drug–drug interaction and offer us some useful strategies for the drug delivery system design.Image 1
