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Accumulating evidence has suggested that curcumin may protect against cerebral ischemia-reperfusion injury (CIRI). However, biological mechanisms vary across studies, limiting the clinical applicability of these findings. We performed a meta-analysis on publications evaluating curcumin administration in rat models of CIRI. Furthermore, we sought to test the hypothesis that curcumin alleviates CIRI through diminishing oxidation and inflammation. We searched PubMed, Embase, Web of Science, and Cochrane from the starting date of each database to May 2022 for experimental rat studies exploring the use of curcumin after ischemia reperfusion. Included articles were assessed for bias using SYRCLE's risk of bias tool. Data were aggregated by a random effects model. Curcumin administration significantly reduced neurological deficit score (20 studies; pooled mean difference [MD] = –1.57; 95% CI, –1.78 to –1.36, P <.00001), infarct volume (18 studies; pooled MD = –17.56%; 95% CI, –20.92% to –14.20%; P < 0.00001), and brain water content (8 studies, pooled MD = -11.29%, 95% CI: -16.48%, -6.11%, P <.00001). Compared with control, the levels of superoxide dismutase, glutathione, and glutathione peroxidase were significantly higher, whereas the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, interleukin-8, and nuclear factor kappa B were significantly lower (P <.05). Subgroup analysis raised the possibility that intervention affections differed by curcumin's dose. To our knowledge, this is the first meta-analysis of curcumin's neuroprotection and mechanisms in rat CIRI models. Our analysis suggests the neuroprotective potential of curcumin in CIRI via antioxidant activity and anti-inflammatory effect. More research is required to further confirm the effectiveness and safety of curcumin on ischemic stroke therapy. A meta-analysis including 29 experimental rat studies reveals curcumin's neuroprotection for cerebral ischemia-reperfusion injury (CIRI) via diminishing oxidation and inflammation in rat models. Indeed, curcumin may be a promising supplementary agent against CIRI. BCCAO, bilateral common carotid artery occlusion; BWC, brain water content; IV, infarct volume; MCAO, middle cerebral artery occlusion; NDE, neurological deficit evaluation. [Display omitted] [ABSTRACT FROM AUTHOR]