One of major challenges in the drug delivery lies in the development of nanoparticles that are effectively delivered to targeted cells and release their payload over an extended period to achieve a clinical response. In this paper, we report a new family of biocompatible and biodegradable polymer, termed polyoxalate that degrades hydrolytically into nontoxic byproducts. Polyoxalate was synthesized from a simple one-step polymerization reaction of 1,4-cyclohexanedimethanol and oxalyl chloride and had a MW of similar to 11000 Da. This polymer was designed to degrade by water hydrolysis into 1,4-cyclohexanedimethanol and oxalic acid, which call be easily removed from a body. Polyoxalate had a hydrophobic backbone and was formulated into nanoparticles with a mean diameter of 600 rim, which is suitable for drug delivery involving phagocytosis by macrophages. Polyoxalate nanoparticles were readily taken tip by RAW 264.7 macrophage cells and HEK (human embryonic kidney) 293 cells and exhibited a minimal cytotoxicity in a time- and dose-dependent manner. In comparison with PLGA nanoparticles, polyoxalate nanoparticles had a significantly higher cell viability. We anticipated that the ease of synthesis and excellent biocompatibility make polyoxalate highly potent for numerous applications in drug delivery.