A mutualistic relationship between the composition, function and activity of the gut microbiota (GM) and the host exists, and the alteration of GM, sometimes referred as dysbiosis, is involved in various immune-mediated diseases, including inflammatory bowel disease (IBD). Accumulating evidence suggests that the GM is able to influence the efficacy of the pharmacological therapy of IBD and to predict whether individuals will respond to treatment. Additionally, the drugs used to treat IBD can modualate the microbial composition. The review aims to investigate the impact of the GM on the pharmacological therapy of IBD and vice versa. The GM resulted in an increase or decrease in therapeutic responses to treatment, but also to biotransform drugs to toxic metabolites. In particular, the baseline GM composition can help to predict if patients will respond to the IBD treatment with biologic drugs. On the other hand, drugs can affect the GM by incrementing or reducing its diversity and richness. Therefore, the relationship between the GM and drugs used in the treatment of IBD can be either beneficial or disadvantageous.