Counteracting reactive oxygen species (ROS, e.g., superoxide radical ion, H2O2 and hydroxyl radical) is an important task in fighting against oxidative stress-related illnesses and in improving product quality in industrial manufacturing processes. This review focuses on the recent advances on two-dimensional (2D) nanomaterials of antioxidant activity, which are designed for effective decomposition of ROS and thus, for reduction of oxidative stress. Some materials featured in this paper are of uni- or multi-lamellar structures modified with small molecular or enzymatic antioxidants. Others are enzyme-mimicking synthetic compounds (the so-called nanozymes) prepared without antioxidant additives. However, carbon-based materials will not be included, as they were extensively reviewed in the recent past from similar aspects. Given the landmark development around the 2D materials used in various bio-applications, sheet-like antioxidant compounds are of great interest in the scientific and technological communities. Therefore, the authors hope that this review on the recent progresses will be helpful especially for researchers working on novel developments to substantially reduce oxidative stress either in biological systems or industrial liquors.