The aim of this review is to address the most up-to-date information on the design and development, structure-activity relationship (SAR), and molecular docking study of novel and effective urease inhibitors between January 2020 and March 2024. Herein, the importance of the substituents and their effect on bioactivity of the reported compounds have been investigated. Besides, the relation between the most important residues inside the active site of the urease enzyme for interactions of the inhibitors and the active site of the enzyme has also been reviewed. This review has been classified into main reported scaffolds, namely, barbiturates, thiobarbiturates, Schiff bases, semicarbazides, thiosemcarbazides, benzimidazoles, 1,3,4-thiadiazoles, and 1,3,4-oxadiazoles, to provide better insight into the newly developed urease inhibitors.