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Bipolar disorder (BD) patients are often accompanied by glycolipid metabolism abnormalities, which reduce disease treatment adherence and increase the risk of cardiovascular disease, bringing certain challenges to current clinical treatment. This retrospective study aims to observe the efficacy of lithium carbonate combined with olanzapine, risperidone, and quetiapine, respectively, in the treatment of BD and its effect on glycolipid metabolism. The 210 patients with BD from Chengdu Jinxin Mental Diseases Hospital were selected between February 2023 and August 2024 and were categorized into LO (Lithium carbonate combined with olanzapine), LR (Lithium carbonate combined with risperidone), and LQ (Lithium carbonate combined with quetiapine) groups according to treatment. The primary outcomes were assessed as changes in the Bech-Rafaelsen mania scale (BRMS) scores, clinical outcomes, and glycolipid metabolism indicators, including triglyceride (TG), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and fasting blood glucose (FBG) in each group. Secondary outcomes included BD severity, measured with the Clinical Global Impression-Bipolar Disorder (CGI-BP) scale, and quality of life, evaluated with the Generic Quality of Life Inventory-74 (GQOLI-74). The indicators of the three groups post-treatment were statistically significant (P < 0.05) compared with the pre-treatment. The LR group had the lowest BRMS scores and CGI-BP-s scores, the highest clinical efficacy, and GQOLI-74 scores. The LO group had markedly increased TC, TG, and LDL levels, while the LR group had markedly increased TG levels, and the LQ group had markedly increased TC and TG levels (P < 0.05). No marked difference in adverse reactions was observed among the three groups (P > 0.05). All three treatment modalities have therapeutic effects on BD, among which LR has remarkable efficacy, significantly improving the patient’s condition and having a relatively small impact on glycolipid metabolism, thus warranting clinical popularization and application.