Periodontitis is a multifactorial and infective oral disease that leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, exploring new therapeutic strategies for a personalized approach is urgent. For this reason, the aim of this study is to summarize recent advances and the potential of oxidative stress biomarkers in the early diagnosis and personalized therapeutic approaches in periodontitis. Recently, ROS metabolisms (ROMs) have been studied in the physiopathology of periodontitis. Different studies show that ROS plays a crucial role in periodontitis. In this regard, the reactive oxygen metabolites (ROMs) started to be searched for the measures of the oxidizing capacity of the plasma understood as the total content of oxygen free radicals (ROS). The oxidizing capacity of plasma is a significant indicator of the body’s oxidant state as well as homocysteine (Hcy), sulfur amino acid, which has pro-oxidant effects as it favors the production of superoxide anion. More specifically, the thioredoxin (TRX) and peroxiredoxin (PRX) systems control reactive oxygen species (ROS), such as superoxide and hydroxyl species, to transduce redox signals and change the activities of antioxidant enzymes to remove free radicals. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), among other antioxidant enzymes, change their activity when ROS are produced in order to neutralize free radicals. The TRX system is triggered and transduces redox signals to do this.