AbstractBackgroundGlobal cerebral ischemia (GCI) is characterized by the hindrance of blood flow to the brain due to obstruction in the carotid arteries. In this study, the neuroprotective effects of berberine chloride (BBR) and cinnamaldehyde (CA) against GCI in male Wistar rats were investigated, and their efficacy was compared.MethodsTwenty‐four rats were randomly assigned to four groups: Sham, GCI, GCI + BBR, and GCI + CA. 100 mg/kg of BBR and CA were administered five minutes and six hours after inducing GCI by occluding two common carotids for 20 minutes.ResultsThe findings showed that both compounds mitigated GCI‐induced damage to the hippocampus and its subfields, and CA demonstrated better neuroprotective efficacy than BBR. These results was also supported by behavioural tests, which revealed better memory function in GCI + CA compared to GCI + BBR.ConclusionThe study showed the neuroprotective impact of CA and BBR against GCI, and CA emerged as a more effective therapeutic agent against GCI‐induced damage. Further research is necessary to uncover the specific mechanisms behind these differences.