Cells are continually exposed to reactive oxygen species (ROS) generated during cellular metabolism. Apoptosis, necrosis, and autophagy are biological processes involving a feedback cycle that causes ROS molecules to induce oxidative stress. To adapt to ROS exposure, living cells develop various defense mechanisms to neutralize and use ROS as a signaling molecule. The cellular redox networks combine signaling pathways that regulate cell metabolism, energy, cell survival, and cell death. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) are essential antioxidant enzymes that are required for scavenging ROS in various cell compartments and response to stressful situations. Among the non-enzymatic defenses, vitamin C, glutathione (GSH), polyphenols, carotenoids, vitamin E, etc., are also essential. This review article describes how ROS are produced as byproducts of oxidation/reduction (redox) processes and how the antioxidants defense system is directly or indirectly engaged in scavenging ROS. In addition, we used computational methods to determine the comparative profile of binding energies of several antioxidants with antioxidant enzymes. The computational analysis demonstrates that antioxidants with a high affinity for antioxidant enzymes regulate their structures.