Asian swamp eel is a freshwater eel covered with a thick layer of mucus. The aim of this study is to evaluate the therapeutic activity of eel skin mucus in-vivo. For in-vivo study, a topical gel delivery system used from eel skin mucus formulated gel to apply into the infected rat skins. Sprague Dawley rats were divided into normal, positive control, negative control, and treated groups. The infections were introduced to the rats by intracutaneous injections of pathogenic bacteria and fungi. The development of impetigo, tinea capitis and cutaneous candidiasis in the animal model was confirmed based on the clinical and histological observations. Following that, the infected rats were treated topically with the formulated gel from eel mucus extract. The histological analysis of the skin tissues which treated with the formulated gel was shown a complete recovery in the skin tissues at a similar rate as the control antibiotic groups. In conclusion, the present study revealed that eelskin mucus formulated gel efficient therapeutic candidate in treating skin infections which can be considered as a novel discovery as a natural alternative treatment for certain skin diseases.