The antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase contribute dominatingly to enhance cellular antioxidant defense against oxidative stress. They act cooperatively to scavenge reactive oxygen species, and not one of them can singlehandedly clear all forms of reactive oxygen species. On the basis of the structural understanding for these natural enzymes, many mimics with multifunctional activities had been obtained by chemical synthesis, biosynthesis, and protein fusion techniques. Some of them display remarkable antioxidant cooperative effect in living model which possess potential application in medicine as potent antioxidants. This review summarizes aspects of some multifunctional mimics which have been reported so far.