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• Table grape supplementation influence the expression of more than 900 human genes. • Microarray analysis supports grape antithrombotic and anti-inflammatory effects. • Grape intake stimulates protective processes such as autophagy and DNA repair. • Mitochondrial biogenesis and cell homeostasis are positively regulated by grape. • Long ncRNAs might be pivotal in regulation of human genes induced by grape. Using a transcriptomic approach, we performed a pilot study in healthy subjects to evaluate the changes in gene expression induced by grape consumption. Blood from twenty subjects was collected at baseline (T0), after 21 days of grape-rich diet (T1) and after one-month washout (T2). Gene expression profiling of peripheral blood mononuclear cells from six subjects identified 930 differentially expressed transcripts. Gene functional analysis revealed changes (at T1 and/or T2) suggestive of antithrombotic and anti-inflammatory effects, confirming and extending previous finding on the same subjects. Moreover, we observed several other favourable changes in the transcription of genes involved in crucial processes such as immune response, DNA and protein repair, autophagy and mitochondrial biogenesis. Finally, we detected significant changes in many long non-coding RNAs genes, whose regulatory functions are being increasingly appreciated. Altogether, our data suggest that a grape diet may exert its beneficial effects by targeting different strategic pathways. [ABSTRACT FROM AUTHOR]