BACKGROUND We investigated the effects of metformin on neurological function and oxidative stress in patients with type 2 diabetes mellitus with acute stroke. MATERIAL AND METHODS We randomly assigned 80 acute stroke patients to 2 groups: the metformin combined group and the insulin group. Each group had 40 patients and all were treated with standard stroke treatment. The indexes of nervous functional score and oxidative stress were measured before and 2 weeks after treatment. The primary fetal rat hippocampal neurons were gradually matured after 7 days of culture, and divided into the control group (Con), the oxygen-glucose deprivation model group (Mod), and the metformin group (Met). In the Met group, 10 mmol/L metformin was added, and the Con group and the Mod group received equal volumes of cell culture fluid. Cell viability, cell apoptosis rate, and the expression of Bax, Bcl-2, AMPK, pAMPK and mTOR were detected; MDA content and SOD activity were also detected. RESULTS Before treatment, there was no difference in the metrical indexes between the 2 groups. After treatment, the treatment group was better than the control group in neurological function scores and multiple oxidative stress-related indicators. The experimental results of primary fetal rat hippocampal neuronal cells suggest that this mechanism of improvement is closely related to the AMPK/mTOR signaling pathway. CONCLUSIONS Metformin can improve the neurological function and oxidative stress status of acute stroke patients with type 2 diabetes, and its mechanism may be related to the AMPK/mTOR signaling pathway and oxidative stress.