BACKGROUND: There has been a growing interest in understanding the effects of social networks on health-related behaviour, with a particular backdrop being the emerging prominence of complexity or systems science in public health. Social network interventions specifically use or alter the characteristics of social networks to generate, accelerate, or maintain health behaviours. We conducted a systematic review and meta-analysis to investigate health behaviour outcomes of social network interventions. METHODS AND FINDINGS: We searched eight databases and two trial registries from 1990 to May 28, 2019, for English-language reports of randomised controlled trials (RCTs) and before-and-after studies investigating social network interventions for health behaviours and outcomes. Trials that did not specifically use social networks or that did not include a comparator group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of health behaviours or outcomes at ≤6 months was assessed by random-effects meta-analysis. Secondary outcomes included those measures at >6-12 months and >12 months. This study is registered with the International Prospective Register of Systematic Reviews, PROSPERO: CRD42015023541. We identified 26,503 reports; after exclusion, 37 studies, conducted between 1996 and 2018 from 11 countries, were eligible for analysis, with a total of 53,891 participants (mean age 32.4 years [SD 12.7]; 45.5% females). A range of study designs were included: 27 used RCT/cluster RCT designs, and 10 used other study designs. Eligible studies addressed a variety of health outcomes, in particular sexual health and substance use. Social network interventions showed a significant intervention effect compared with comparator groups for sexual health outcomes. The pooled odds ratio (OR) was 1.46 (95% confidence interval [CI] 1.01-2.11; I2 = 76%) for sexual health outcomes at ≤6 months and OR 1.51 (95% CI 1.27-1.81; I2 = 40%) for sexual health outcomes at >6-12 months. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in haemoglobin A1c (HbA1c), and smoking cessation. Because of clinical and measurement heterogeneity, it was not appropriate to pool data on these other behaviours in a meta-analysis. For sexual health outcomes, prespecified subgroup analyses were significant for intervention approach (p < 0.001), mean age of participants (p = 0.002), and intervention length (p = 0.05). Overall, 22 of the 37 studies demonstrated a high risk of bias, as measured by the Cochrane Risk of Bias tool. The main study limitations identified were the inclusion of studies of variable quality; difficulty in isolating the effects of specific social network intervention components on health outcomes, as interventions included other active components; and reliance on self-reported outcomes, which have inherent recall and desirability biases. CONCLUSIONS: Our findings suggest that social network interventions can be effective in the short term (<6 months) and longer term (>6 months) for sexual health outcomes. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in HbA1c, and smoking cessation.