Drawbacks of poly(ethylene glycol) (PEG), the most widely used water-soluble polymer in nanomedicines, have stimulated development of alternative hydrophilic polymers. Among the substitutes, poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) exhibits water solubility, minimal toxicity, and the possibility to introduce functionalities through pendant hydroxyl groups; however, nondegradability may cause long-term health and environmental issues. Alternatively, polycarbonates based on bis-MPA derivatives, which are well-known to be biocompatible, biodegradable, and of low toxicity in vivo, could be utilized as degradable equivalents to polymethacrylates. Therefore, we developed a polycarbonate-based PHPMA analogue, poly(S-methyl-5-(2-hydroxypropyl)aminocarbonyl-1,3-dioxan-2-one) (PMHPAC), by amidation of carboxylic acid-functional polycarbonates with 1-amino-2-propanol. The resulting PMHPAC was highly water-soluble, with low cyto-/immunotoxicities, and readily functionalizable. These characteristics make PMHPAC a promising candidate as a degradable alternative to PEG and PHPMA. Furthermore, a fully degradable PMHPAC block copolymer was synthesized to demonstrate synthetic versatility and formation of nanostructures in aqueous solution for potential biomedical applications.