Cellular metabolic changes during chronic kidney disease (CKD) may induce higher production of oxygen radicals that play a significant role in the progression of renal damage and in the onset of important comorbidities. This condition seems to be in part related to dysfunctional mitochondria that cause an increased electron "leakage" from the respiratory chain during oxidative phosphorylation with a consequent generation of reactive oxygen species (ROS). ROS are highly active molecules that may oxidize proteins, lipids and nucleic acids with a consequent damage of cells and tissues. To mitigate this mitochondria-related functional impairment, a variety of agents (including endogenous and food derived antioxidants, natural plants extracts, mitochondria-targeted molecules) combined with conventional therapies could be employed. However, although the anti-oxidant properties of these substances are well known, their use in clinical practice has been only partially investigated. Additionally, for their correct utilization is extremely important to understand their effects, to identify the correct target of intervention and to minimize adverse effects. Therefore, in this manuscript, we reviewed the characteristics of the available mitochondria-targeted anti-oxidant compounds that could be employed routinely in our nephrology, internal medicine and renal transplant centers. Nevertheless, large clinical trials are needed to provide more definitive information about their use and to assess their overall efficacy or toxicity.