The rising incidence of ischemic stroke poses significant health and healthcare burdens. Given the limitations of current therapeutic options, there is increasing interest in exploring the potential of galangin, a natural flavonoid compound, as a treatment for ischemic stroke. This study aimed to evaluate the neuroprotective effects and underlying mechanisms of galangin in mitigating oxidative stress, inflammation, and apoptosis in a rat model of permanent cerebral ischemia. Sixty male Wistar rats were divided into six groups: control; right middle cerebral artery occlusion (Rt.MCAO) with vehicle; Rt.MCAO with piracetam, a synthetic compound known as a cognitive enhancer; and Rt.MCAO with galangin administered at doses of 25, 50, and 100 mg/kg body weight. Neurological deficit scores, brain edema, neuronal density, and microglial morphology were assessed along with the activity of myeloperoxidase (MPO), a marker of inflammation, and superoxide dismutase (SOD). Additionally, the expression of key markers for inflammation and apoptosis, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), Bcl-2-associated X protein (Bax), B-cell lymphoma-extra large (Bcl-XL), and caspase-3, was analyzed to elucidate potential mechanisms. The results demonstrated that galangin treatment significantly improved neurological deficit scores, reduced brain edema, enhanced neuronal density, attenuated microglial activation, decreased MPO activity, and increased SOD activity in both the cortex and hippocampus, highlighting its neuroprotective potential. These effects were linked to the modulation of inflammatory and apoptotic pathways. Specifically, galangin significantly reduced the expression of IL-6, COX-2, Bax, and caspase-3 while increasing the levels of the anti-apoptotic protein Bcl-XL. In conclusion, galangin demonstrates significant promise as a neuroprotective agent for ischemic stroke by suppressing inflammation and apoptosis, thereby improving neurological outcomes. However, clinical trials are required to validate these preclinical findings and confirm galangin’s therapeutic efficacy in humans.