Objective <p>To observe the clinical efficacy of acupuncture and moxibustion plus traditional Chinese herbs in treating depression after ischemic stroke and its effects on monoamine neurotransmitter levels.</p> Methods <p>A total of 80 patients with depression after ischemic stroke were divided into a control group and an observation group using the random number table method, with 40 cases in each group. The two groups were treated with Wen Yang Jie Yu Tang (decoction for warming Yang and relieving depression). The observation group was treated with additional acupuncture and moxibustion therapy. The therapeutic effect was evaluated after 4 weeks of treatment. The traditional Chinese medicine (TCM) main symptoms and depression symptoms were scored before and after 4 weeks of treatment. Neurological function was assessed using the National Institutes of Health stroke scale (NIHSS), depressive symptoms were evaluated by the 17-item Hamilton depression scale (HAMD-17), and sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Meanwhile, the serum levels of monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), noradrenaline (NE), and dopamine (DA), were measured. The incidence of adverse reactions during treatment was compared between the two groups.</p> Results <p>The total effective rates in improving depression symptoms and TCM main symptoms in the observation group were both higher than those in the control group (<i>P</i>&lt;0.05). After treatment, the scores of each TCM main symptom, NIHSS, HAMD-17, and PSQI in both groups were all lower than those before treatment (<i>P</i>&lt;0.05), and the scores in the observation group were lower than those in the control group (<i>P</i>&lt;0.05). After 4 weeks of treatment, the serum levels of 5-HT, NE, and DA in both groups were all higher than those before treatment (<i>P</i>&lt;0.05), and the serum levels in the observation group were higher than those in the control group (<i>P</i>&lt;0.05). During the treatment period, there was no statistical difference in the incidence of adverse reactions between the two groups (<i>P</i>&gt;0.05).</p> Conclusion <p>The treatment of acupuncture and moxibustion plus traditional Chinese herbs has significant efficacy in treating depression after ischemic stroke; it can effectively relieve the symptoms, improve neurological function and sleep quality, increase monoamine neurotransmitter levels, and has high safety.</p>