Ascorbic acid is a well-known antioxidant widely used in cosmetics, pharmaceuticals, and food products. However, its hydrophilic nature limits its effectiveness to the aqueous phase, making it challenging to harness its full potential in complex formulations. To overcome these limitations, lipophilic derivatives such as ascorbyl palmitate have been developed to extend its antioxidant activity beyond monophasic systems. Despite the known antioxidant benefits of vitamin C, only a limited number of studies has directly compared the impact of its hydrophilic and lipophilic forms on emulsion stability and oxidative resistance. This study investigates the effects of hydrophilic (ascorbic acid, AA) and lipophilic (ascorbyl palmitate, AP) forms of vitamin C on the oxidative stability, physicochemical properties, and cytocompatibility of oil-in-water nanoemulsions of natural products designed for topical applications. Nanoemulsions were formulated with poppyseed oil as the oil phase, incorporating standardized concentrations of AA or AP. The emulsions were characterized for droplet size (∼200 nm, PDI < 0.3), zeta potential (below −30 mV), Newtonian rheological behavior, antioxidant activity, and thermal stability. Additionally, in vitro cytocompatibility was assessed using THP-1 monocytes to evaluate immunogenic responses. Our findings demonstrate that the antioxidative potency of ascorbic acid exceeds that of ascorbyl palmitate when assessed using the DPPH assay. This study highlights the importance of carefully controlling formulation parameters to maintain the beneficial properties of natural oils. Furthermore, it shows that both antioxidant forms are suitable for the topical application of the poppy seed oil-based nanoemulsion.