Single-atom nanozymes (SAzymes) with excellent biological catalytic activity have emerged as promising candidates for advancing biomedical applications. Herein, we synthesized a RuN4-SAzyme by thermal decomposition. In in vitro experiments, the RuN4-SAzyme demonstrated exceptional catalytic efficiency in mimicking the activity of peroxidase, with a Michaelis-Menten constant (Km) for 3,3',5,5'-tetramethylbenzidine reaching 0.077 mM, reflecting a high substrate affinity. Moreover, the RuN4-SAzyme also exhibited catalase- and superoxide dismutase-like activities, as well as nicotinamide adenine dinucleotide oxidase-like activity, effectively neutralizing reactive oxygen species. Significantly, in vivo experiments demonstrated that RuN4-SAzymes can effectively alleviate eczema-like symptoms by clearing inflammatory factors, reducing oxidative stress, and promoting macrophage polarization from M1 to M2, showing comparable efficacy to the clinical drug tacrolimus.