Small molecule antioxidants have little impact on oxidative stress in vivo because of their poor bioavailability. To explore an antioxidant for in vivo applications, a polymeric antioxidant containing a ferrocene moiety was developed. The ferrocene-containing monomer was synthesized through the robust tricomponent Biginelli reaction with a high yield. The corresponding water-soluble copolymer was conveniently prepared via radical polymerization. Both the ferrocene moiety and the Biginelli structure (dihydropyrimidin-2(H)-one) contributed to the remarkable radical scavenging ability of this highly biocompatible copolymer. It was more efficient than traditional small molecule antioxidants at protecting cells against fatal oxidative stress. This copolymer also showed clear therapeutic activity in counteracting oxidation-induced acute liver damage in a live mouse model. Our study into functional organometallic polymers resulted in a promising polymeric biomaterial that may find therapeutic applications and have important implications in the fields of organic chemistry and polymer chemistry.