The aqueous ethanolic extract of Salsola imbricata (AEESI) demonstrated significant protective effects against UV-C radiation damage, using earthworms and isopods as models for human skin and eyes, respectively. High-performance liquid chromatography (HPLC) analysis identified 15 bioactive polyphenolic compounds in AEESI, with chlorogenic acid (55.51 µg/ml) and gallic acid (46.69 µg/ml) as the dominant phenolic acids, and naringenin (40.42 µg/ml) as the primary flavonoid. The extract effectively mitigated histological and ultrastructural damage caused by UV-C radiation in both models. Additionally, quality control parameters, including moisture content, pH, acidity index, ash content, and elemental composition, were determined for the first time. These findings highlight the potential of S. imbricata extract as a protective agent against UV-C radiation-induced damage, attributed to its rich polyphenolic content.