This study aimed to investigate the effects of fluoxetine on swallowing function, neurotrophic factors, and psychological status in patients with dysphagia after acute ischemic stroke (AIS). A total of 118 patients with dysphagia after AIS who were diagnosed and treated in our hospital from July 2020 to March 2022 were selected as the study objects with 59 cases in each group. Patients in the control group underwent routine treatment and swallowing rehabilitation without fluoxetine. Patients in the study group received routine treatment, swallowing rehabilitation, and fluoxetine treatment. The quality of life was compared according to the Generic Quality of Life Inventory-74 (CQOLI-74). Patients were followed for 90 days, and the grades were compared with the Modified Rankin Scale (mRS). The total effective rate of the study group was 84.75%, which was higher than that of the control group with 62.71% (χ2 = 7.394, P < 0.05). The life quality scores of the two groups were both dramatically elevated compared to those before the treatment, and the study group had a sensibly higher life quality score than the control group (P < 0.05). The proportion of grade 4~5 in the study group was significantly lower than that in the control group (χ2 = 492, P < 0.05). The total incidence of adverse reactions in the control group was 5.08% (3/59), which was significantly lower than that in the study group with 11.86% (7/59) (χ2 = 1.748, P = 0.186). Fluoxetine has a significant effect on the treatment of dysphagia after AIS by enhancing the recovery of dysphagia and promoting the recovery of neurological function.