Abstract: Ischemic stroke (IS) is a disease with high mortality and disability rate worldwide, and there are few clinical treatment drugs. The natural active ingredients of traditional Chinese medicine, such as cinnamaldehyde and anisaldehyde, have antioxidant and anti-inflammatory effects, which can reduce the oxidative stress injury caused by ischemic stroke. In addition, studies have found that L-arginine is a substrate of nitric oxide synthase (NOS), which can be converted into NO in the body to dilate blood vessels and increase blood flow in the cerebral ischemic area. In this paper, 10 new L-arginine/active aldimine derivatives were designed and synthesized, and the neuroprotective effects of ischemic stroke were evaluated biologically. The results of oxygen glucose deprivation/reperfusion (OGD/R) cell model showed that the cell survival rate of the arginine imine derivative AI-2 group formed by L-arginine and 2-methoxycinnamaldehyde was higher than that of the positive drug butylphthalide (NBP) group, and it could effectively release L-arginine, significantly reduce the levels of reactive oxygen species and malondialdehyde, increase the level of superoxide dismutase, and had a high antioxidant effect. The results of in vivo experiments showed that AI-2 (5 mg·kg^-1) could significantly improve the neurological function score of transient middle cerebral artery occlusion model in rats and effectively reduce cerebral infarction, which was superior to butylphthalide. In this study, a class of L-arginine/active aldimine derivatives with neuroprotective activity were found, which provided lead compounds for the treatment of ischemic stroke. All operations in the experiment were approved by the Animal Ethics Committee of China Pharmaceutical University, approval No. YSL-202503102.