Urea transporters (UTs) facilitate the rapid transport of urea from the extracellular space to the intracellular space through a selective transport mechanism driven by urea concentration gradients. Advances in Cryo-electron microscopy and X-ray crystallography have enabled us to solve the homotrimer structures of UT-A and UT-B, which share a common feature comprising two homologous domains surrounding a continuous transmembrane pore, indicating that UTs transport urea via a channel-like mechanism. By analyzing the structures of ligand-protein complexes, results from molecular dynamics simulations, and functional data on urea analogues and small molecule permeation inhibitors, we can gain a deeper understanding of the conservation and specificity of the urea channel architecture, and clearly recognize how urea is transported by UTs and the mechanisms of small molecule inhibition. This will provide an important structural basis for drug design and development.