Different enzymatic and non-enzymatic antioxidants counteract oxidative stress caused by reactive oxygen species, protecting cells, tissues, and organs from harm. Reactive oxygen species, or free radicals, are produced as byproducts of several health-related activities and are always present in the body. Antioxidant mechanisms eliminate them from the body under normal circumstances. When these defense systems are compromised, radicals build up excessively and play a role in the onset of several illnesses. Oxidative stress is the outcome of an imbalance between the production and neutralization of oxidants, and it leads to the onset of several illnesses, disorders, and aging. During critical illness, oxidative stress and inflammation serve as physiological response mechanisms to various stressors and damage. Oxidative stress can result from any dysregulation of these systems. Clinical manifestations of long-term oxidative stress can include neurological diseases, cancer, cardiovascular problems, metabolic disorders including chronic kidney disease, chronic obstructive pulmonary disease, and diabetes. The influence of oxidative stress on human health is examined in this chapter with a focus on the underlying oxidants, processes, and routes. To develop efficient natural medicinal treatments for both prevention and treatment, it also covers the mechanism of ROS-induced oxidative stress signaling and the age-associated problems mediated through their toxic manifestations. The human body’s antioxidant defense mechanism limits the amount of inflammation and oxidative stress under normal circumstances; however, critically sick individuals frequently have drastically reduced antioxidant capacities. Therefore, giving critically ill patients antioxidants and anti-inflammatory foods may help to lessen the severity of oxidative stress and enhance their clinical results. The chapter concludes that the developing area of redox medicine requires a deep understanding of cellular redox processes.