BackgroundA large body of literature associated extra virgin olive oil (EVOO) consumption with low risk of cardiovascular disease and mortality. However, findings from clinical trials related to EVOO consumption on blood pressure, lipid profile, and anthropometric and inflammation parameters are not univocal. ObjectivesThe aim of this systematic review and meta-analysis was to evaluate the effect of EVOO consumption on cardiometabolic risk factors and inflammatory mediators. MethodsWe searched PubMed/MEDLINE, Scopus, and Cochrane up through 31 March, 2023, without any particular language limitations, in order to identify randomized controlled trials (RCTs) that examined the effects of EVOO consumption on cardiometabolic risk factors, inflammatory mediators, and anthropometric indices. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge’s g and random-effects modeling. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). ResultsThirty-three trials involving 2020 participants were included. EVOO consumption was associated with a significant decrease in insulin (n = 10; SMD: −0.28; 95% CI: −0.51, −0.05; I2 = 48.57%) and homeostasis model assessment of insulin resistance levels (HOMA-IR) (n = 9; SMD: −0.19; 95% CI: −0.35, −0.03; I2 = 00.00%). This meta-analysis indicated no significant effect of consuming EVOO on fasting blood glucose, triglycerides, total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins, Apolipoprotein (Apo) A-I and B, lipoprotein a, blood pressure, body mass index, waist circumference, waist to hip ratio, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor α levels (P > 0.05). ConclusionsThe present evidence supports a beneficial effect of EVOO consumption on serum insulin levels and HOMA-IR. However, larger well-designed RCTs are still required to evaluate the effect of EVOO on cardiometabolic risk biomarkers.This study was registered in PROSPERO as CRD42023409125.