Intracerebral hemorrhage (ICH) represents a significant health challenge due to its high mortality and severe outcomes. Poly (ADP-ribose) polymerase (PARP) is a chromatin-associated nuclear protease, which would be activated by ROS derived from hematoma metabolites after ICH, and lead to parthanatos, a form of caspase-independent programmed cell necrosis. Recent evidence indicates that PARP activation plays a pivotal role in various human diseases, particularly neurodegenerative disorders, cerebral ischemia–reperfusion injury, and hemorrhagic transformation. However, the link between PARP activation and secondary brain injury (SBI) following ICH remains underexplored. This review delves into the pathological mechanisms of PARP activation in cell injury, with a focus on parthanatos, mitochondrial dysfunction, neuroinflammation, and blood–brain barrier (BBB) disruption after ICH. Understanding these processes may offer new insights into the role of PARP activation in ICH and pave the way for developing more effective therapeutic strategies.