Objective: To explore and analyze the effect of escitalopram oxalate (EO) combined with mirtazapine in patients with bipolar depression based on symptom control and cognitive function improvement. Methods: The research subjects were 100 patients with bipolar depression admitted to the Beijing Fangshan mental health center from June 2021 to June 2025. They were divided into the experimental group (n=50) and the reference group (n=50) by the sealed envelope lottery method. The reference group was treated with EO, while the experimental group was treated with EO combined with mirtazapine. The efficacy, clinical symptoms, cognitive function, sleep quality, and adverse reactions of the two groups were compared. Results: In terms of the total effective rate, the experimental group was higher than the reference group (P<0.05). Eight weeks after administration, the scores of the Hamilton depression scale (HAMD) and the Young mania rating scale (YMRS) in both groups were lower than those before administration, and the scores of the experimental group were lower than those of the reference group (all P< 0.05). Eight weeks after administration, the scores of complete classification and correct response in the experimental group were higher than those in the reference group, while the scores of incorrect response and persistent error were lower than those in the reference group (all P<0.05). Eight weeks after administration, the PSQI scores of both groups were lower than those before administration, and the scores of the experimental group were lower than those of the reference group (all P<0.05). The incidence of adverse reactions between the two groups was not significantly compared (P>0.05). Conclusion: EO combined with mirtazapine can significantly improve the symptoms, cognitive function and sleep quality of patients with bipolar depression.