Acovenoside A, a cardenolide glycoside from Acokanthera oppositifolia, demonstrates significant therapeutic potential in cardioprotection and oncology, particularly against non-small cell lung cancer (NSCLC). However, its toxicological profile requires thorough evaluation for safe pharmaceutical application. For this purpose a comprehensive in silico methods were applied, including ACD/Labs Percepta, STopTox, admetSAR 3.0, ADMETlab 3.0, ProTox 3.0, TEST 5.1.2, and VEGA QSAR, for prediction of a key toxicological endpoints (acute toxicity, potential health effects, skin and eye irritation, as well as endocrine disruption). These different methods and models were applied to build a comprehensive toxicological profile for Acovenoside A, synthesizing predictions to inform its potential risks and guide future research. The qualitative toxicity predictions using in silico tools (STopTox, admetSAR 3.0) shows specific structural fragments responsible for toxicity (toxicophores) and high probabilities (89.3-90 %) of acute toxicity depending on route of exposure. Quantitative acute toxicity predictions (Percepta, ProTox 3.0, Test 5.1.2, VEGA QSAR) indicated moderate to high toxicity, with LD