This chapter aims at investigating the efficacy of iron oxide (Fe2O3) nanoparticles as fillers for gold standard orthopedic biomaterial, i.e., ultrahigh-molecular-weight PE (UHMWPE). Green synthesis root is used for obtaining iron oxide nanoparticles from Punica granatum fruit peel extract. The synthesized nanoparticles by this root are pure with band gap energy equal to 1.81 eV and have a high degree of crystalline structure with average crystalline size of 37.71 nm as confirmed by UV-VIS spectroscopy and XRD, respectively. Subsequent to preparation of Fe2O3 nanoparticles, UHMWPE nanocomposite are prepared with 1%, 3%, and 5% (by weight) of Fe2O3 nanoparticles. These composites are irradiated with gamma radiation with dosages of 25 kGy and 50 kGy, respectively. After irradiation, the composites are assessed with FTIR spectroscopy to the probe the structural changes and oxidation strength by estimating oxidation index (OI) values. The characteristic peaks at 2913 cm−1 and 2845 cm−1 are assigned as sp3 C-H stretching of PE 730 cm−1 belongs to iron oxide, 1461 cm−1 is identified to C-H bending, respectively. The free radical quenching ability of green-synthesized Fe2O3 nanoparticles along with UHMWPE is evident from the OI values, which is lowest for UHMWPE/Fe2O3 nanocomposite. The specialty for choosing the Fe2O3 nanoparticles is that these particles are highly biocompatible and thus used for overcoming the degradation of structure in material along with UHMWPE.