Objective To study the changes in metabolic markers and clinical outcome after treatment with different drug regimens in children with bipolar affective disorder. Methods A retrospective analysis was performed on the medical data of 220 children with bipolar affective disorder who attended the hospital from January 2017 to January 2020. According to the treatment method, 112 children treated with atypical antipsychotic drugs alone were enrolled as the control group, and 108 children treated with atypical antipsychotic drugs combined with mood stabilizer were enrolled as the study group. The two groups were compared in terms of baseline data, changes in related metabolic markers[fasting insulin (FIN), glycosylated hemoglobin (HbAlc), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after treatment, incidence rate of metabolic syndrome, and clinical outcome. Results There were no significant differences in the baseline data including age, sex, and course of disease between the two groups (P > 0.05). The study group had a significantly higher overall response than the control group (92.6% vs 82.1%, P < 0.05). Before treatment, there were no significant differences in the levels of FIN and HbAlc between the two groups (P > 0.05). After treatment, the control group had a significant increase in the level of FIN and a significantly higher level of FIN than the study group (P < 0.05). The study group showed no significant change in the level of FIN after treatment (P > 0.05). There was no significant difference in the level of HbAlc between the two groups before and after treatment (P > 0.05). Before treatment, there were no significant differences in the levels of TC, TG, HDL-C, and LDL-C between the two groups (P > 0.05), and after treatment, the control group had significant increases in TC and TG and significantly higher levels of TC and TG than the study group (P < 0.05). The study group showed no significant changes in TC and TG after treatment (P > 0.05). There were no significant differences in the levels of HDL-C and LDL-C between the two groups before and after treatment (P > 0.05). The study group had a significantly lower incidence rate of metabolic syndrome than the control group (2.8% vs 9.8%, P < 0.05). Conclusions Atypical antipsychotic drugs combined with mood stabilizer in the treatment of bipolar disorder in children have little effect on the level of metabolic markers, and the curative effect is significant.