Skin lesions caused by ultraviolet radiation exposure seriously reduce people's life quality, safe natural products development to prevent and repair ultraviolet damage is an effective strategy. We investigated the protective and reparative effects of the natural composite gel (SE-gel) derived from fish scales on UV-irradiated skin by inhibiting reactive oxygen species (ROS) -mediated oxidative stress and inflammatory responses. Our results showed that SE-gel rich in glycine and proline had good ultraviolet absorption, water absorption, moisturizing and free radical scavenging abilities. In vitro, SE-gel could improve UV-irradiated L929 cell viability by 1.24 times via inhibiting 50% ROS production and malondialdehyde, and improving superoxide dismutase activity to reduce oxidative stress caused by UV irradiation. In UV-irradiated mouse skin damage model, SE-gel prevent UV-induced skin erythema, epidermal thickening, collagen fiber degradation and disruption, and reduced UV-induced inflammatory response via NF-κB signaling pathway, showing potential application in UV-irradiated skin damage prevention and repair.