To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy.