Biodegradable polymers have gained enormous attentions in the pharmaceutical and biomedical applications, especially in drug delivery. In this work, we report the synthesis and characteristics of high molecular weight polyoxalate with ~75000 Da. Hydrolytic degradation kinetics and degradation products were characterized by nuclear magnetic resonance and gel permeation chromatography. Polyoxalate is a semicrystalline and thermally stable polymer with a glass transition temperature of , which is suitable for drug delivery applications. The hydrophobic nature of polyoxalate allows it to be formulated into nanoparticles and encapsulate drugs using a conventional oil-in-water emulsion/solvent displacement method. Polyoxalate nanoparticles also exhibited excellent cytotoxicity profiles. It can be suggested that polyoxalate has great potential for numerous biomedical and pharmaceutical applications.