Metabolic Syndrome (MetS) augments the incidence of cardiovascular disease by two-fold and type II diabetes mellitus by five-fold. Montmorency tart cherries are rich in phytochemicals shown to improve biomarkers related to cardio-metabolic health in humans. This study aimed to examine cardio-metabolic responses after 7-days Montmorency tart cherry juice (MTCJ) supplementation and also acute on short-term supplementation responses to a single bolus, in humans with MetS. In a randomised, single-blind, placebo-controlled, crossover trial, 12 participants with MetS (50 ± 10years; 6M/6F), consumed MTCJ or placebo (PLA) for 7days. Blood-based and functional cardio-metabolic biomarkers were measured pre- and post-supplementation, and acute responses measured pre-bolus and up to 5h post-bolus on the 7th day. 24-h ambulatory systolic (P = 0.016), diastolic (P = 0.009) blood pressure and mean arterial pressure (P = 0.041) were significantly lower after 7-days MTCJ supplementation compared to PLA. Glucose (P = 0.038), total cholesterol (P = 0.036), LDL (P = 0.023) concentrations, total cholesterol:HDL ratio (P = 0.004) and respiratory exchange ratio values (P = 0.009) were significantly lower after 6-days MTCJ consumption compared to PLA. This study revealed for the first time in humans that MTCJ significantly improved 24-h BP, fasting glucose, total cholesterol and total cholesterol:HDL ratio, and also lowered resting respiratory exchange ratio compared to a control group. Responses demonstrated clinically relevant improvements on aspects of cardio-metabolic function, emphasising the potential efficacy of MTCJ in preventing further cardio-metabolic dysregulation in participants with MetS. Registered at clinicaltrials.gov (NCT03619941).