Aim: The occurrence and progression of intervertebral disc degeneration (IDD) are significantly influenced by the cartilaginous endplate (CEP). Pinocembrin (PIN), a type of flavonoid present in propolis and botanicals, demonstrates both antioxidant and anti-inflammatory characteristics, which could potentially be utilized in management. Therefore, it is crucial to investigate how PIN protects against CEP degeneration and its mechanisms, offering valuable insights for IDD therapy., Materials and Methods: To investigate the protective impact of PIN in vivo, we created the IDD mouse model through bilateral facet joint transection. In vitro, an IDD pathological environment was mimicked by applying TBHP to treat endplate chondrocytes., Key Findings: In vivo, compared with the IDD group, the mouse in the PIN group effectively mitigates IDD progression and CEP calcification. In vitro, the activation of the Nrf-2 pathway improves the process of Parkin-mediated autophagy in mitochondria and decreases ferroptosis in chondrocytes. This enhancement promotes cell survival by addressing the imbalance of redox during pathological conditions related to IDD. Knocking down Nrf-2 with siRNA fails to provide protection to endplate chondrocytes against apoptosis and degeneration., Significance: The Nrf-2-mediated activation of mitochondrial autophagy and suppression of ferroptosis play a crucial role in safeguarding against oxidative stress-induced degeneration and calcification of CEP through the protective function of PIN. To sum up, this research offers detailed explanations about how PIN can protect against apoptosis and calcification in CEP, providing valuable information about the development of IDD and suggesting possible treatment approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)