Nickel as heavy metal can generate free radicals directly from molecular oxygen in a two step process to produce O2.-. The ROS, as they react to majority of the organism molecules, are able to interfere with the biological processes causing several diseases, mutations, aging and the other alterations in the body. The balance between the oxidant and antioxidant species will able to obtain the conditions to a better performance of its functions, considering that a disturbance in this balance can result in a range of pathological process. L-ascorbic acid is hydro soluble and act like reducing agent (electron donor) and also acts against the free radicals including singlet oxygen. The ?-tocopherol, situated near the cytochrome P450 (cyt P450) in the membrane phospholipid, sweep the free radicals formed in cyt P450. Research findings in author’s laboratory on nickel toxicities and protective role of L-ascorbic acid and ?-tocopherol to stabilize endogenous antioxidant status are discussed in details in this book.