WD repeat-containing protein 5 (WDR5) is a member of the WD40 protein family, and it is widely involved in various biological activities and not limited to epigenetic regulation in vivo. WDR5 is also involved in the initiation and development of many diseases and plays a key role in these diseases. Since WDR5 was discovered, it has been suggested as a potential disease treatment target, and a large number of inhibitors targeting WDR5 have been discovered. In this review, we discussed the development of inhibitors targeting WDR5 over the years, and the biological mechanisms of these inhibitors based on previous mechanistic studies were explored. Finally, we describe the development potential of inhibitors targeting WDR5 and prospects for further applications.