Abstract: Objective To explore the clinical efficacy of lamotrigine combined with electroencephalogram (EEG) biofeedback in the treatment of depressive episodes in adolescents with bipolar disorder. Methods A total of 160 adolescent patients with bipolar disorder experiencing depressive episodes admitted to the Seventh People's Hospital of Wenzhou City from January 2023 to October 2024 were selected. They were numbered according to the order of admission and randomly assigned to a control group and an intervention group, with 80 patients in each. The control group received olanzapine and lamotrigine treatment, while the intervention group received additional EEG biofeedback therapy alongside the same regimen. The efficacy differences between the two groups were compared. Results After 12 weeks of treatment, the clinical efficacy of the intervention group was superior to that of the control group (P ＜ 0.05). At 8- and 12-week of treatment, the levels of serum brain-derived neurotrophic factor (BDNF), γ-aminobutyric acid (GABA), and cognitive function scores in the intervention group were higher than those in the control group. The levels of homocysteine (Hcy), depression score, mania, and social function score were lower than those in the control group (P ＜ 0.05). Compared with pre-treatment baseline, the above aforementioned indicators and scores of both groups showed significant improvement in both groups (P ＜ 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05). Conclusion The combination of EEG biofeedback therapy and lamotrigine can significantly alleviate depressive mood and improve cognitive function in adolescent patients with bipolar disorder during depressive episodes. It effectively controls manic symptoms, promotes the recovery of social functioning, and beneficially modulates serum biomarker levels. This combined approach demonstrates high clinical efficacy and a favorable safety profile.