This study aimed to investigate the neuroprotective effects of zingerone (ZGN) against pentylenetetrazol (PTZ) -induced oxidative stress, inflammation, and apoptosis in SH-SY5Y neuronal cells, focusing on the involvement of the PARP-1/TRPM2 signalling pathway. SH-SY5Y cells were exposed to PTZ (30 μM, 24 h) with or without ZGN pretreatment (5–25 μM). Cell viability was assessed by CCK-8 assay, while oxidative stress (MDA, GSH) and inflammatory (IL-1β, TNF-α) markers were quantified by ELISA. Apoptotic responses were assessed through caspase-3/9 activity assays. TRPM2 and PARP-1 protein expression were determined by Western blot analysis. PTZ exposure significantly decreased cell viability and increased MDA, IL-1β, TNF-α, and caspase-3/9 activities, as well as TRPM2 and PARP-1 expression (p<0.05). ZGN treatment significantly reversed these changes in a dose-dependent manner, reducing oxidative stress, apoptosis, and inflammation. ZGN provides potent neuroprotection against PTZ-induced cell damage by inhibiting the PARP-1/TRPM2 signalling axis, thereby reducing oxidative stress, cytokine release, and caspase activation. These findings suggest that ZGN may be a promising agent for targeting TRPM2-mediated oxidative neurotoxicity in neurodegenerative disorders.