Rational design of metallic active sites and its microenvironment is critical for constructing superoxide dismutase (SOD) nanozymes. Here, we reported a novel SOD nanozyme design, with employing graphene oxide (GO) as the framework, and δ-MnO₂ as the active sites, to mimic the natural Mn-SOD. This MnO₂@GO nanozyme exhibited multiscale laminated structures with honeycomb-like morphology, providing highly specific surface area for ·O ⁻₂ adsorption and confined spaces for subsequent catalytic reactions. Thus, the nanozyme achieved superlative SOD-like catalytic performance with inhibition rate of 95.5%, which is 222.6% and 1605.4% amplification over GO and MnO₂ nanoparticles, respectively. Additionally, such unique hierarchical structural design endows MnO₂@GO with catalytic specificity, which was not present in the individual component (GO or MnO₂). This multiscale structural design provides new strategies for developing highly active and specific SOD nanozymes.