Oxidative stress can result from diminished antioxidant protection as well as increased free radical production. A sophisticated enzymatic [including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] and non-enzymatic [glutathione, vitamins A, C, and E, and some minerals] antioxidant defense system counteract and regulates overall ROS levels to maintain physiological homeostasis. In addition to this internal antioxidant defense system, it is important to consider the role of exogenous antioxidants from the diet, such as polyphenols and carotenoids, among others bioactive compounds. A great body of evidence tries to elucidate the role of these compounds in the protection of plant-derived foods against degenerative diseases. Thereby, in this review recent studies in cellular, animal and human models will be described, which evaluate the role of polyphenols and carotenoids in the antioxidant defense system against oxidative stress through the modulation of the antioxidant enzymes. Studies reviewed show that the antoxidant enzyme response to normal or oxidative stress situations depends on the enzyme involved, the animal specie or cell line selected, in addition to the features of the intervention or treatment carried out (doses, length, and design of experiments). The most abundant model in these studies has been the animal model due to its ability of being model of induced oxidative stress. In most of the studies when oxidative stress arises, the treatment, supplementation or intervention done prevent or attenuate the decrease in the antioxidant enzyme. Further research is needed to clarify how dietary polyphenols and carotenoids modulate cellular antioxidant enzyme concentrations and how they contribute to regulate the molecular mechanisms and cellular signaling pathways.