Oxidative stress is a pathological condition that has been implicated as a central player in a variety of diseases, including vascular and neurodegenerative diseases. More recently, oxidative stress has also been shown to be involved in the biological incompatibility of many materials especially at the nanoscale. As such, there is a critical need for new biomaterials that can inhibit this response, improving the compatibility of medical devices. In this work, trolox, a synthetic antioxidant and water-soluble analogue of Vitamin E, is polymerized to form an oxidation active polymer as a new class of biomaterial. Synthesized poly(trolox ester) polymers were formulated into nanoparticles using a single emulsion technique, and their size was controlled by changing the polymer concentration in the organic solvent. Nanoparticle cytotoxicity, protective effects against cellular oxidative stress, and degradation kinetics were all evaluated. Poly(trolox ester) nanoparticles were found to have little to no cytotoxicity and were capable of suppressing cellular oxidative stress induced by cobalt nanoparticles. In vitro degradation studies of poly(trolox ester) nanoparticles indicate that the antioxidant activity of nanoparticles was derived from its enzymatic degradation to release active antioxidants.