The skin is among the largest organs in the human body. In contrast to epithelial tissue, which comprises the epidermis, connective tissue comprises the dermis. Oxidative stress arises from the daily exposure of the epidermis to numerous detrimental elements. Skin integrity and homeostasis are compromised when cellular defenses against reactive oxygen species fail to maintain equilibrium with antioxidant defenses. To effectively stimulate skin immunological responses to stress, it is critical to consider the skin microbiota, immune and nonimmune cells, and the skin itself. The growing need for new molecules that can influence immunological processes in the skin has led to increased development efforts, especially in the area of compounds produced from natural products. This chapter discusses various kinds of natural antioxidants that have been demonstrated to influence skin immunological responses, along with their mechanisms of action and capacity. It also covers the application of antioxidants in skincare, limitations and future prospects.