Increasing evidence uncovers the involvement of gut microbiota in the metabolism of numerous pharmaceutical drugs. The human gut microbiome harbours 10-100 trillion symbiotic gut microbial bacteria that utilize drugs as substrates for enzymatic processes to alter host metabolism. Thus, microbiota-mediated drug metabolism can change the conventional drug action course and cause inter-individual differences in efficacy and toxicity, making it vital for drug discovery and development. This review focuses on drug biotransformation pathways and discusses different models for evaluating gut microbiota role in drug metabolism.