Abstract: Objective To investigate the effects and mechanisms of maca alkaloids on neural regeneration and cognitive function in rats with ischemia-reperfusion injury. Methods A total of 42 SD male rats (7 weeks old) were randomly divided into three groups: sham operation group, model group, and maca alkaloid treatment group. A middle cerebral artery occlusion (MCAO) model was established using the intraluminal suture method. The Morris water maze test was used to evaluate behavioral and cognitive functions. The levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activity in the blood, liver, and hippocampal tissues were detected by commercial kits. An oxygen-glucose deprivation/reperfusion (OGD/R) model with C17.2 neural stem cells was established to simulate ischemic stroke in vitro. Cell proliferation was assessed by immunofluorescence staining and CCK-8 assay. The levels of neuron marker tubulin, astrocyte marker glial fibrillary acidic protein (GFAP), and oligodendrocyte marker 2', 3'-cyclic nucleotide phosphodiesterase (CNP) were measured by Western blot to evaluate neural stem cell differentiation. Results Compared with the model group, rats in the maca alkaloid treatment group exhibited a significantly reduced escape latency, elevated path efficiency, and increased platform crossings (P<0.05), with more streamlined swimming trajectories. In the treatment group, the GSH and SOD levels in the blood, liver, and hippocampal tissues significantly increased, but MDA levels remarkably decreased, compared with those in the model group (P<0.05). Immunofluorescence staining and CCK-8 assay results showed that maca alkaloids promoted C17.2 cell proliferation. Western blot results indicated that maca alkaloids markedly enhanced GFAP expression (P<0.05), with no significant effect on tubulin or CNP expression (P>0.05). Conclusions Maca alkaloids alleviate oxidative stress induced by cerebral ischemia-reperfusion injury, promote the proliferation of neural stem cells and their differentiation into astrocytes, and improve cognitive impairment caused by ischemia-reperfusion injury.