The Golgi apparatus (GA) is a critical membranous organelle involved in intracellular trafficking and signal transduction. Under physiological conditions, the GA functions in concert with the endoplasmic reticulum to process, sort, and transport newly synthesized proteins and lipids, ensuring that these biomolecules are accurately modified and delivered to their appropriate cellular destinations. The maintenance of GA homeostasis is essential for physiological cellular function and adaptation to environmental changes. Any disruption in this homeostasis can lead to cellular dysfunction and even death. This review summarizes and deliberates on the latest advances in understanding the significance of GA homeostasis in regulating programmed cell death, and explores its involvement in neurodegenerative diseases, cancer, and infectious diseases, uncovering the potential mechanismsunderlying GA in the regulation of signal transduction.