Inflammatory bowel disease (IBD) is a chronic and recurring lifelong condition, the exact etiology of which remains obscure. However, an increasing corpus of research underscores the pivotal role of cellular signaling pathways in both the instigation and management of intestinal inflammation. Drosophila, owing to its prodigious offspring, abbreviated life cycle, and the conservation of signaling pathways with mammals, among other advantages, has become a model organism for IBD research. This review will expound on the feasibility of utilizing Drosophila as an IBD model, comparing its intestinal architecture with that of mammals, its inflammatory responses, and signaling pathways. Furthermore, it will deliberate on the role of natural products across various biological models of IBD pathways, elucidating the viability of fruit flies as IBD models and the modus operandi of cellular signaling pathways in the context of IBD.