Human skin undergoes changes during aging that result from the synergistic effects of intrinsic and extrinsic factors that may culminate in wrinkle formation, a characteristic of aged skin. Panax ginseng and ginsenosides have promising properties in preventing skin aging. Our previous study demonstrated that enzyme-modified ginseng extract (EG) has inhibitory effects against ultraviolet B (UVB) radiation-induced skin aging. The purpose of the current study was to evaluate the preventive effects of EG on eye-wrinkle formation by applying EG cream in 23 randomized human subjects. Compared to the placebo, EG significantly reduced the global photo-damage score. In addition, total roughness (R1), smoothness depth (R4), and arithmetic roughness average (R5) were significantly decreased with use of EG. In a post-study questionnaire, subjects responded that EG was absorbed efficiently into the skin and was more potent in moisturizing and softening skin than the placebo. No participants reported adverse reactions to treatment. In conclusion, EG sufficiently suppressed eye wrinkle formation by decreasing various roughness measures on the basis of assessment with non-invasive devices. Therefore, our results indicate that EG is a promising anti-aging candidate that could be used as an ingredient in natural functional food and cosmetic products.