In recent years, naturally biodegradable polyhydroxyalkanoate (PHA) monopolymers have become focus of public attentions due to their good biocompatibility. However, due to its poor mechanical properties, high production costs, and limited functionality, its applications in materials, energy, and biomedical applications are greatly limited. In recent years, researchers have found that PHA copolymers have better thermal properties, mechanical processability, and physicochemical properties relative to their homopolymers. This review summarizes the synthesis of PHA copolymers by the latest biosynthetic and chemical modification methods. The modified PHA copolymer could greatly reduce the production cost with elevated mechanical or physicochemical properties, which can further meet the practical needs of various fields. This review further summarizes the broad applications of modified PHA copolymers in biomedical applications, which might shred lights on their commercial applications. In recent years, naturally biodegradable polyhydroxyalkanoate (PHA) monopolymers have become the focus of public attention due to their good biocompatibility. This review summarizes the synthesis of a range of PHA copolymers by the latest biosynthetic and chemical modification methods. This review further summarizes the broad application of modified PHA copolymers in biomedical applications and highlights its latest applications in biomedical applications. This article is part of an AFOB (Asian Federation of Biotechnology) Special issue. To learn more about the AFOB visit www.afob.org.