Polycystic kidney disease (PKD) is a common hereditary renal disorder characterized by abnormal proliferation and dilation of renal tubular cysts, which can eventually lead to renal failure. Currently, drug screening plays a pivotal role in PKD therapeutic research, but traditional cell and animal models exhibit significant limitations in mimicking disease complexity and screening efficiency, failing to meet clinical needs. In recent years, organoid models, as innovative in vitro research tools, have demonstrated unique advantages and enormous application potential by precisely simulating the three-dimensional structure, pathological features, and patient-specific characteristics of PKD. This article systematically reviewed the research status of PKD drug screening models, covering the construction and application of cell models, animal models, organoid models, and cutting-edge technologies such as organ-on-a-chip. Through typical case analyses and multi-model comparisons, the characteristics of different models were analyzed in-depth, and the core value of organoid models in high-throughput drug screening, precision medicine practice, and personalized therapy exploration was explicitly highlighted. Studies have confirmed that organoid models can effectively compensate for the shortcomings of traditional models, holding promise as key tools to drive breakthroughs in PKD therapeutic research and opening new pathways for clinical translation. Meanwhile, this article scientifically prospects the future development directions of organoid models in the field of PKD research, aiming to provide references and inspiration for follow-up studies.