Abstract: Oxidative stress is suggested as the root cause of aging and various human diseases like atherosclerosis, diabetes, cancer, stroke and neurodegenerative diseases. Researchers are advocating enrichment of body systems with antioxidants-the free-radical scavenging molecules, to correct vitiated homeostasis and prevent the onset as well as treat the disease caused/promoted due to free radicals and related oxidative stress. Antioxidants are also known to induce biosynthesis of other antioxidants or defense enzymes. Various studies and trials on antioxidant’s potential as drugs are being carried out in the research community. Advance efforts are made to elucidate the importance of antioxidant therapy based on drug discovery from natural products like plants, animals, microalgae and microbes, isolation of active principles and further modification and refinement of active antioxidant molecules. Numerous antioxidants like superoxide dismutase, genistein, ellagic acid, epigallocatechin-3-O-gallate, indole-3-carbinol, lycopene, coenzyme Q10, quercetin, vitamin C and vitamin E have been found to be pharmacologically active. This review presents insights of the role of antioxidants in various diseases and their potential to act and contribute as efficient drug candidates for treatment of related diseases. The novel biomolecules that can be of benefit and act as novel antioxidant-based drug formulations for the treatment and prevention of complex diseases like Alzheimer’s disease (AD), cancer, Parkinson's disease, rheumatoid arthritis, diabetes and neurodegenerative diseases are discussed and the scope with strategic development of newer therapies using them are explored.