Antioxidation is in demand in living systems, as the excessive reactive oxygen species (ROS) in organisms lead to a variety of diseases. The conventional antioxidation strategies are mostly based on the introduction of exogenous antioxidants. However, antioxidants usually have shortcomings of poor stability, non-sustainability, and potential toxicity. Here, we proposed a novel antioxidation strategy based on ultra-small nanobubbles (NBs), in which the gas–liquid interface was employed to enrich and scavenge ROS. It was found that the ultra-small NBs (~ 10 nm) exhibited a strong inhibition on oxidization of extensive substrates by hydroxyl radicals, while the normal NBs (~ 100 nm) worked only for some substrates. Since the gas–water interface of the ultra-small NBs is non-expendable, its antioxidation would be sustainable and its effect be cumulative, which is different to that using reactive nanobubbles to eliminate free radicals as the gases are consumptive and the reaction is unsustainable. Therefore, our antioxidation strategy based on ultra-small NB would provide a new solution for antioxidation in bioscience as well as other fields such as materials, chemical industry, food industry, etc.