IntroductionDepression is a pervasive mental health challenge with substantial global ramifications. Contemporary therapeutic strategies predominantly consist of psychological interventions and pharmacological treatments. Acupuncture, deeply rooted in ancient traditions and bolstered by a plethora of clinical trials, demonstrates considerable efficacy in depression. This study aims to elucidate the efficacy and safety of acupuncture as a standalone therapy for depression patients by reviewing randomized controlled trials that compare acupuncture treatment with conventional drug therapy.MethodsComprehensive searches were conducted across six databases in both Chinese and English: CNKI, Wanfang, VIP, Embase, Medline, and CENTRAL. The literature search spanned from 1 July 2013, to 1 July 2023. Two researchers independently carried out literature screening and data extraction. Review Manager 5.4 was utilized for data analysis and bias risk assessment. A total of 20 randomized controlled trials were included in the qualitative synthesis, involving 1,376 participants and 43 relevant acupoints.ResultsThe Meta-analysis results, based on the HAMD scale scores, revealed that acupuncture regimens (RR: −1.63; 95% CI: −2.49 to −0.76; P = 0.0002; I2 = 86%; n = 1,668) were significantly more effective compared to standalone medication. Moreover, efficacy metrics from the HAMD highlighted a substantial advantage of acupuncture (RR: 2.6; 95% CI: 1.6 to 4.23; P = 0.0001; I2 = 0; n = 614). Further assessments utilizing SERS and TESS demonstrated a lower incidence of side effects and adverse outcomes in the acupuncture group.ConclusionsAcupuncture, when compared to conventional pharmacotherapy, exhibits significant efficacy as a standalone treatment after four weeks of intervention, with fewer side effects and adverse reactions. However, further investigation is needed to determine the most effective acupoints and appropriate types of acupuncture techniques for treating depression.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023443711.