Objective To explore the changes in serum insulin-like growth factor-1（ IGF-1） and cyclic glycine proline（ cGP） levels in patients with acute ischemic stroke（ AIS）， and their value in assessing the prognosis of neurological function in patients with AIS within three months. Methods A total of 132 patients with AIS admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from June 2022 to March 2023 were selected for the study. Modified Rankin Scale（ mRS）， National Institute of Health Stroke Scale（ NIHSS）， and Barthel Index（ BI） were used to assess the severity of the patient's condition and prognosis. Patients were categorized into 80 cases in good prognosis group（ mRS≤2） and 52 cases in poor prognosis group（ mRS≥3） based on the mRS score at three months after the onset of the disease. Serum IGF-1 and cGP levels were measured using enzyme-linked immunosorbent assay（ ELISA） at the time of admission and 7 days after admission in both groups. Spearman correlation was used to analyze the correlation of serum IGF-1，cGP levels and cGP/IGF-1 molar ratio with clinical outcomes（ NIHSS score， mRS score and BI score）. Factors influencing poor prognosis were analyzed by binomial Logistic regression with 3-month poor prognosis（ yes/ no=1/0） as the dependent variable and serum levels of IGF-1 and cGP as the independent variables， and the strength of correlation of the 3-month prognostic factors in patients with AIS was determined using the receiver operating characteristic（ ROC） curve. Results At the time of admission and at 7 days of admission， the cGP levels in poor prognosis group were 9.49（ 6.48， 10.91） ng/ml， 8.10（ 6.93， 12.00） ng/ml， and the cGP/IGF-1 molar ratios were 1.67（ 0.94， 2.40） and 1.50（ 1.11， 2.26）， which were higher than those in good prognosis group of 4.45（ 2.78， 6.42） ng/ml， 4.62（ 3.66， 5.20） ng/ml and 1.03（ 0.31， 1.76），0.72（ 0.51， 0.79）， and the differences were statistically significant（ Z=-3.189，-3.777，-3.023，-3.952；all P＜ 0.01）. Serum cGP levels and cGP/ IGF-1 molar ratios were positively correlated with mRS scores after three months， with statistically significant differences（ r=0.400， P=0.005； r=0.597， P ＜ 0.001； r=0.348， P=0.015； r=0.603， P ＜ 0.001）. Binomial Logistic regression analysis showed elevated serum cGP levels at admission［ adjusted OR=1.467， 95%CI （1.099，1.957）， P=0.009］ and cGP levels at 7 days of admission［ adjusted OR=1.723， 95%CI（ 1.194，2.485）， P=0.004］， and increased cGP/IGF-1 molar ratio at admission［ adjusted OR=4.198， 95%CI（ 1.392，12.655）， P=0.011］ and cGP/IGF-1 molar ratio at 7 days of admission［ adjusted OR=15.892， 95%CI（ 2.536，99.576）， P=0.003］ were all risk factors for 3-month poor prognosis of AIS patients. The area under the ROC（ AUC） for serum cGP and cGP/IGF-1 molar ratio at 7 days of admission was 0.818 and 0.833， respectively. The cGP/IGF-1 molar ratio AUC was maximal with a critical value of 0.829. Conclusions Elevated serum cGP levels and cGP/ IGF-1 molar ratios in AIS patients are independently associated with poor functional outcomes. Serum cGP levels and cGP/IGF-1 molar ratios can be used as important biomarkers to assess AIS prognosis.