Publisher Summary Molecules in biological systems often perform more than one function. Many structures have the ability to scavenge free radicals, acting in living organisms as antioxidants, although their main biological function is different. During oxidative stress, the increase in the concentration of these molecules seems to be a biological response that in synergism with the other antioxidant defense systems may protect cells from oxidation. Among these structures, chondroitin sulfate (CS) has increasingly attracted the interest of many research groups. This chapter discusses the action of CSs in reducing molecular damage caused by free radicals and associated oxygen reactants. The chondroitin‐4‐sulfate exerts higher antioxidant activity than chondroitin‐6‐sulfate. The specific sulfation pattern seems to play a central role in the inhibitory activity of these molecules on free radicals because the suggested mechanism is entrapment by the chelation of those metal cations, such as Fe2+ and Cu2+, which, in turn by Fenton's reaction, are responsible of reactive oxygen species production. Chondroitin sulfate's protection on a wide variety of molecules (i.e., lipids, proteins, and DNA) and in various cells from different organs is documented in several in vitro and in vivo experimental studies.