The demand for high-quality seafood products is constantly growing worldwide. Nevertheless, seafood is susceptible to rapid rancidity mainly due to lipid oxidation and microbiological spoilage. Thus, treatment with antioxidants offers a preservation technique that can prolong the shelf life of seafood. However, because of food safety and health concerns about the use of synthetic antioxidants, there is growing interest in the application of natural antioxidants, mainly plant extracts and compounds, as an alternate means of confronting the problem of lipid oxidation. In this review, up-to-date information and recent discoveries about different naturally occurring antioxidants on the oxidation progress, synthetic antioxidants and their health concerns, health benefits of antioxidants, antioxidants used for seafood, and food safety concerns are addressed. The antibacterial effects of natural antioxidants are also reviewed. Finally, the most effective methods for analyzing a wide range of antioxidants in plants are described.