Due to their precise three-dimensional structures and tunable cavities, metallacages and covalent cages have been widely used in various fields, such as catalysis, separation, sensing, and biomedicine. As a result of the unique pattern of directed synthesis and modular assembly, cages can be modified in many different ways to construct stimuli-responsive cages for marker detection and imaging in biological applications. Additionally, imaging agents and drugs can be loaded into the unique cavity of the cages to achieve precise disease diagnosis and treatment. This Review summarizes recent advances in metallacages and covalent cages in biological applications and presents their representative examples in imaging and therapeutics. The problems and future development directions of cages in biological applications are emphasized, which may provide clear guidance for the design and application of precise and controllable biological diagnostic reagents.