Coeliac disease (CeD) is an immune-mediated disorder characterised by gluten-triggered inflammation and damage in the small intestine, with lifelong gluten-free diet (GFD) as the only treatment. It is a multifactorial disease, involving genetic and environmental susceptibility factors, and its complexity and lack of comprehensive human model systems have hindered understanding of its pathogenesis and development of new treatments. Therefore, it is crucial to establish systems that recapitulate patient genetic background and the interactions between the small intestinal epithelial barrier, immune cells, and environment that contribute to CeD. In this review, we discuss disease complexity, recent advances in stem cell biology, organoids, tissue co-cultures, and organ-on-chip (OoC) systems that facilitate the development of comprehensive human model systems, and model applications in preclinical studies of potential treatments.