IBD is a complex multifactorial inflammatory disease of the gut driven by extrinsic and intrinsic factors, including host genetics, the immune system, environmental factors and the gut microbiome. Technological advancements such as next-generation sequencing, high-throughput omics data generation and molecular networks have catalysed IBD research. The advent of artificial intelligence, in particular, machine learning, and systems biology has opened the avenue for the efficient integration and interpretation of big datasets for discovering clinically translatable knowledge. In this narrative review, we discuss how big data integration and machine learning have been applied to translational IBD research. Approaches such as machine learning may enable patient stratification, prediction of disease progression and therapy responses for fine-tuning treatment options with positive impacts on cost, health and safety. We also outline the challenges and opportunities presented by machine learning and big data in clinical IBD research., Competing Interests: Competing interests: BV received lecture fees from Abbvie, Ferring Pharmaceuticals, Janssen, R-Biopharm and Takeda; consultancy fees from Janssen and Sandoz. SV: research grant: MSD, AbbVie, Takeda, Pfizer, J&J; lecture fee: MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche; consultancy: MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche, Celgene, Mundipharma, Celltrion, SecondGenome, Prometheus, Shire, Prodigest, Gilead, Galapagos. SV is a senior clinical investigator of the Research Foundation–Flanders (FWO). The work of MM and TK is supported by BenevolentAI, and TK’s work is also supported by Unilever., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)