The recognition-directed host-guest interaction is recognized as a valuable tool for creating supramolecular polymers. Functional hydrogels constructed through the dynamic and reversible host-guest complexation are endowed with a great many appealing features, such as superior self-healing, injectability, flexibility, stimuli-responsiveness and biocompatibility, which are crucial for biological and medicinal applications. With numerous topological structures and host-guest combinations established previously, recent breakthroughs in this area mostly focus on further improvement and fine-tuning of various properties for practical utilizations. The current contribution provides a comprehensive overview of the latest developments in hostguest supramolecular hydrogels, with a particular emphasis on the innovative molecular-level design strategies and hydrogel formation methodologies targeting at a wide range of active biomedical domains, including drug delivery, 3D printing, wound healing, tissue engineering, artificial actuators, biosensors, etc. Furthermore, a brief conclusion and discussion on the steps forward to bring these smart hydrogels to clinical practice is also presented.