Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a “healthier profile” and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.