This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: -4.83 kg, 95%-CI: -5.46, -4.21; n = 6 RCTs), waist circumference (MD: -1.73 cm, 95%-CI: -3.69, 0.24; n = 2), fat mass (MD: -2.54 kg, 95%-CI: -3.78, -1.31; n = 6), triacylglycerols (MD: -0.20 mmol/L, 95%-CI: -0.38, -0.03; n = 5) and systolic blood pressure (MD: -6.11 mmHg, 95%-CI: -9.59, -2.64; n = 5). No effects were observed for LDL-cholesterol, fasting glucose, and glycosylated-hemoglobin. Both, IER and CER have similar effect on body weight (MD: -0.55 kg, 95%-CI: -1.01, -0.09; n = 13), and fat mass (MD: -0.66 kg, 95%-CI: -1.14, -0.19; n = 10), and all other outcomes. In conclusion, IER improves anthropometric outcomes and intermediate disease markers when compared to a usual diet. The effects of IER on weight loss are similar to weight loss achieved by CER.