〔Abstract〕 Objective To investigate the clinical efficacy of vitamin B12 combined with folic acid in the treatment of ischemic stroke and the effect on plasma homocysteine (Hcy) level. Methods A total of 136 patients with ischemic stroke admitted to Sanmenxia Central Hospital from July 2020 to March 2022 were selected as the study objects and divided into conventional group (66 cases) and combined group (70 cases) according to different treatment methods. Patients in the conventional group received standardized treatment for ischemic cerebrovascular disease, and the combined group received vitamin B12 tablets and folic acid tablets in addition to the conventional group. Both groups were treated for 4 weeks. Plasma levels of Hcy, folic acid and vitamin B12, scores of National Institute of Health stroke scale (NIHSS) and activity of daily living (ADL) before and after treatment were compared between the two groups, and recurrent stroke events during the follow-up period were recorded. Results Before treatment, there was no significant difference in plasma Hcy, folic acid, vitamin B12, NIHSS and ADL scores between the two groups (P > 0.05). After treatment, the plasma Hcy level of the combined group was lower than that of the conventional group, while the plasma folic acid and vitamin B12 levels were higher than that of the conventional group, the differences were statistically significant (P < 0.05). After treatment, ADL score in the combination group was higher than that in the conventional group, and NIHSS score was lower than that in the conventional group, and the differences were statistically significant (P < 0.05). During the follow-up period, the recurrence rate of patients in the combination group was 6.67 %, lower than 26.67 % in the conventional group, and the difference was statistically significant (P < 0.05). Conclusion In the treatment of ischemic brain stroke, the combination of vitamin B12 and folic acid can improve the plasma levels of Hcy, folic acid and vitamin B12, improve the clinical therapeutic effect, reduce the degree of neurological impairment, improve the ability of daily living activities, and reduce the recurrence rate.