MicroRNAs (miRNAs) represent important tools in medicine and nutrition as new biomarkers, and can act as mediators of nutritional and pharmacological interventions. The aim of the present study was to analyse the effect of grape pomace supplementation on the expression of seven selected miRNAs and their potential relationship with the observed positive effect on glycaemic control, in order to shed light on the mechanism underlying the beneficial effect of this dietary intervention. For this purpose, plasma samples were obtained from 49 subjects with metabolic syndrome. After supplementation with grape pomace (6 weeks), these subjects were categorised as responders (n = 23) or non-responders (n = 26) according to the changes in their fasting insulin rate. MiRNA expression at baseline and at the end of the supplementation was analysed by RT-PCR, and the MiRecords Database was used to identify potential target genes for the studied miRNAs. The increase observed in miR-23a in the whole cohort was present in both subgroups of participants. The increase in miR-181a was significant among non-responders but not responders. The decrease in miR-30c and miR-222 was found in the responders, but not in the non-responders. No changes were observed in miR-10a, miR-151a, miR-181a, and miR-let-7a expressions. After analysing these results, a potential involvement of the reduced expression of miR-30c and miR-222, two microRNAs associated with insulin resistance and diabetes, in the improvement of glycaemic control produced by grape pomace administration, can be proposed. Further research is needed to confirm the involvement of glycolytic enzymes, PI3K, AMPK, and IRS-1 in the effect of grape pomace, as suggested by the changes induced in microRNAs.