BACKGROUND & AIMS: Fasting and energy-restricted diets have been evaluated in several studies as a means of improving cardiometabolic biomarkers related to body fat loss. However, further investigation is required to understand potential alterations of leptin and adiponectin concentrations. Thus, we performed a systematic review and meta-analysis to derive a more precise estimate of the influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans, as well as to detect potential sources of heterogeneity in the available literature. METHODS: A comprehensive systematic search was performed in Web of Science, PubMed/MEDLINE, Cochrane, SCOPUS and Embase from inception until June 2019. All clinical trials investigating the effects of fasting and energy-restricted diets on leptin and adiponectin in adults were included. RESULTS: Twelve studies containing 17 arms and a total of 495 individuals (intervention = 249, control = 246) reported changes in serum leptin concentrations, and 10 studies containing 12 arms with a total of 438 individuals (intervention = 222, control = 216) reported changes in serum adiponectin concentrations. The combined effect sizes suggested a significant effect of fasting and energy-restricted diets on leptin concentrations (WMD: -3.690 ng/ml, 95% CI: -5.190, -2.190, p </= 0.001; I(2) = 84.9%). However, no significant effect of fasting and energy-restricted diets on adiponectin concentrations was found (WMD: -159.520 ng/ml, 95% CI: -689.491, 370.451, p = 0.555; I(2) = 74.2%). Stratified analyses showed that energy-restricted regimens significantly increased adiponectin (WMD: 554.129 ng/ml, 95% CI: 150.295, 957.964; I(2) = 0.0%). In addition, subsequent subgroup analyses revealed that energy restriction, to </=50% normal required daily energy intake, resulted in significantly reduced concentrations of leptin (WMD: -4.199 ng/ml, 95% CI: -7.279, -1.118; I(2) = 83.9%) and significantly increased concentrations of adiponectin (WMD: 524.04 ng/ml, 95% CI: 115.618, 932.469: I(2) = 0.0%). CONCLUSION: Fasting and energy-restricted diets elicit significant reductions in serum leptin concentrations. Increases in adiponectin may also be observed when energy intake is </=50% of normal requirements, although limited data preclude definitive conclusions on this point.