Abstract Background Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. Methods Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4–6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. Results Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. Conclusions Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.