Herein, a new class of main chain functionalized aliphatic polycarbonates with sulfur/selenium functional groups on the backbone is reported. Sulfur/selenium‐containing cyclic carbonate monomers (MR) are designed and synthesized by enzyme‐catalyzed intermolecular macro‐ring closure of related diols. The proposed synthetic strategy is tolerant of other functionalities such as N‐substituted groups. The ring opening polymerization (ROP) of MR occurs readily as a versatile route to generate a new family of main chain sulfur/selenium substituted aliphatic polycarbonates (PR) with predictable molecular weights (MW), narrow molecular‐weight distribution and controlled copolymer composition. The resultant polymers can be oxidized and/or reduced by treatment with hydrogen peroxide (H2O2) or dithiothreitol (DTT), highlighting their potential for applications in the stimuli‐responsive field and inflammation/cancer targeting. With these desirable results, it is revealed that this versatile technique can provide a broad‐reaching method to the next generation of innovative materials, especially, well‐defined biodegradable chalcogen‐based main chain functional biomaterials.