ETHNOPHARMACOLOGICAL RELEVANCE: The seed of Aesculus wilsonii Rehd., also known as Suoluozi in China, is a traditional Chinese herb included in the Pharmacopoeia of China (2020). Sodium aescinate (SA) is derived from the Aesculus wilsonii Rehd.'s seeds and is extensively used in clinical practice. AIM OF THE STUDY: The study investigated the involvement of the Nrf2/CTH pathway in SA-induced hepatotoxicity and explored potential strategies for alleviating SA-induced liver damage. MATERIALS AND METHODS: The ICR mice and AML12 mouse hepatocytes were exposed to SA. The levels of Fe RESULTS: SA triggered ferroptosis and apoptosis in AML12 cells and mouse livers, characterized by a decline in Cys, GSH, and H CONCLUSIONS: SA triggers oxidative stress, mitochondrial dysfunction, apoptosis, and ferroptosis, ultimately leading to liver damage by suppressing the Nrf2/CTH pathway.