Gold nanomaterials have attracted increasing attention in biomedical applications due to their biocompatibility and intrinsic optical and physicochemical properties. Oxidative stress, which is mainly contributed by reactive oxygen species (ROS), has been crucial in various cancers and diseases. Here, we report a gold nanodandelion (GND)-based ROS-scavenging system using the antioxidant properties of GNDs. GNDs scavenge superoxide anions and hydroxyl radicals in situ and induce oxidative etching with hydrogen peroxide (H 2 O 2 ). The size and surface passivation of gold nanomaterials regulated the efficiency of ROS scavenging. The differential effect of GNDs to scavenge intracellular ROS was studied through cell viability, nanoparticle uptake, ROS production, and antioxidant enzymes. Results indicated that GNDs in normal fibroblasts and macrophages display minimal toxicity and provide protection from H 2 O 2 -induced oxidative stress. For the first time, GNDs exhibit outstanding nitric oxide (NO • ) generation performance in M1 macrophage. Interestingly, the presence of GNDs in glioma cells attenuated cell proliferation, migration, and invasion behaviors. GNDs are expected to be a promising antioxidant in cancer treatment and tumor microenvironment modulation.