Biocompatible or biodegradable hyperbranched polymers (HBPs), an important subclass of hyperbranched macromolecules, have recently received an increasing attention due to their unique physical and chemical properties as well as their great advantages in therapeutic applications. This review highlights recent advances and future trends in the preparation and applications of biocompatible or biodegradable HBPs for therapeutic purpose. Various biocompatible or biodegradable hyperbranched structures can be obtained by means of step-growth polycondensation (SGP), self-condensing vinyl polymerization (SCVP), self-condensing ring-opening polymerization (SCROP), and so forth. The properties of biocompatible or biodegradable HBPs can be tailored for a specialized purpose through terminal modification, backbone modification, or hybrid modification. A particular emphasis is then placed on their diagnostic, therapeutic delivery and theranostic applications. Finally, future directions and perspectives in this emerging field are briefly discussed. These developments on synthesis and therapeutic applications of biocompatible or biodegradable HBPs promote the interdisciplinary research spanning polymer materials and biomedical sciences.