Objective To investigate the effect of citicoline sodium combined with aluminum magnesium aspirin on neurological function recovery and serum levels of biomarkers associated with neural injury and repair in patients with mild ischemic stroke not receiving thrombolysis, and to evaluate its clinical safety.Methods From January 2023 to September 2025, the 113 patients with mild ischemic stroke not receiving thrombolysis at our hospital were included. Using a random number table, participants were allocated to a control group (56 patients) or an observation group (57 patients). Both groups received standard treatment, including control of blood pressure, blood glucose, and blood lipid levels, as well as rehabilitation training. The control group received aluminum magnesium aspirin tablets in addition to standard treatment, whereas the observation group received citicoline sodium tablets in addition to the treatment administered to the control group. Both groups were treated continuously for 3 months. The degree of neurological deficit [National Institutes of Health Stroke Scale (NIHSS), Neurobehavioral Cognitive Status Examination (NCSE) ], cognitive function [Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) ], activities of daily living [Barthel Index (BI) ], serum biomarkers of neural injury [homocysteine (Hcy), brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), S100β protein], adverse reactions, and cardio-cerebrovascular adverse events were compared between the two groups.Results After 3 months of treatment, the observation group showed lower NIHSS scores and higher NCSE scores, scores of each MoCA domain and total MoCA scores, total MMSE scores, and BI scores compared with the control group (P < 0.05). The levels of Hcy, NSE, and S100β were lower, whereas the level of BDNF was higher in the observation group than in the control group (P < 0.05). The changes from baseline in NIHSS scores, NCSE scores, scores of each MoCA domain and total MoCA scores, total MMSE scores, BI scores, and serum levels of Hcy, BDNF, NSE, and S100β were greater in the observation group than in the control group (P < 0.05). No significant differences were observed between the two groups in the overall incidence of adverse reactions or the overall incidence of cardio-cerebrovascular adverse events (P > 0.05).Conclusion Compared with antiplatelet therapy with aluminum magnesium aspirin alone, the addition of citicoline sodium more effectively improves neurological deficits and cognitive impairment, enhances activities of daily living, and reduces serum levels of biomarkers of neural injury in patients with mild ischemic stroke not receiving thrombolysis, with good safety. This combined therapeutic strategy provides new evidence for optimizing neurorestorative approaches in patients with mild stroke.