Drosophila melanogaster has been widely used as a model organism to study the pathogenesis of various human diseases. Despite significant morphological differences between the kidneys of mammals and Drosophila, both maintain a level of conservation in the regulatory mechanisms in kidney development and renal function. As a result, Drosophila has emerged as an ideal model for investigating the pathogenesis of human kidney diseases and for the rapid screening of potential therapeutic drugs. The mammalian kidney is composed of nephrons, including glomerulus, renal capsule and renal tubule, while the Drosophila renal sys-tem consists of nephrocytes and Malpighian tubules. In terms of function, nephrocytes are equivalent to glomeruli, and Malpighian tubules are equivalent to renal tubules. The development and function of the Drosophila renal system is regulated by multiple genetic factors. The proteins such as immunoglobulin super-family (IgSF) and Krüppel-like factor 15 (Klf15), and the JAK-STAT signaling pathway are crucial to the mor-phological formation of the Drosophila renal system, and the genes Cubilin, Amnionless, and rudhira are es-sential for its functions. This review summarizes the kidney structure, development and regulation in mam-mals and Drosophila, and discusses the advantages and future prospects of using the Drosophila model to study human kidney-related diseases.