The construction of metal-organic frameworks (MOFs) by mixed-bridging organic ligands represents an important and widely used strategy for the design and synthesis of MOFs with a higher level of complexity, which shows advantages in the discovery of new topologies, multiple-step self-assembly, and anisotropic modification on pore sizes and shapes. This article summarizes important advances in MOFs with mixed-bridging organic ligands, covering the design and synthetic methods, structures, and properties.