Many marine mollusca secrete sulfuric and hydrochloric acids as a defensive mechanism. Herein, we investigated the histological and histochemical abnormalities of skin acid secretion (SAS) extract toxicity of the sea slug Berthellina citrina after oral administration in mice and toads comparatively, including the spleen, liver, stomach, ileum, and kidney. This study also investigated whether vitamin E (Vit. E) could reduce the toxic effects of SAS. The treated spleens of mice and toads with SAS showed atrophy in the white pulp, a decrease in the splenocyte density, megakaryocytes cytoplasmic degeneration, inflammatory cell infiltration and the number of white and red pulp splenocytes decreased. Additionally, the megakaryocyte size increased compared to the control. The treated liver sections of mice and toads also exhibited general inflammation, fibrosis, vasodilation, and angiogenesis. The treated stomachs of mice and toads showed degeneration in the mucosal layer. The treated ileum of mice and toads showed lamina propria detattachment, leukocyte infiltration, and enlargement of villi size. Furthermore, the kidneys of mice treated with SAS showed shrinkage in glomeruli size while toads exhibited enlargement. This demonstrates the potential toxicity of SAS. Vit. E was induced as a protective dose along with SAS administration. Vit. E was able to reduce the adverse effects of SAS extract in both mice and toads. Additionally, this study showed that, Vit. E can protect against SAS-induced toxicity. Generally, Vit. E improved hemoglobin, leukocytes, and lymphocytes number. This study showed important data about the toxicity of SAS and the ameliorative role of Vit. E in reducing SAS side effects.