We examined the ability of tomato pomace extract (by-product) to affect platelet aggregation in healthy humans (clinical pilot study). In phase 1 the tolerance of participants (n = 15; 5 per dose level) ingesting tomato pomace extract across three dose levels (1, 2.5, and 10 g) was evaluated. Phase 2 was a single-blind, placebo-controlled, parallel design human (male, n = 99; 33 per group) pilot intervention trial investigating the acute and repeated dose effects (5 days) of different doses of tomato pomace extract (1 g, 2.5 g or placebo) on platelet aggregation ex vivo. Various flavonoids (coumaric acid, floridzin, floretin, procyanidin B2, luteolin-7-O-glucoside, kaempferol, and quercitin) and nucleosides (adenosine, inosine, and guanosine) were identified in the tomato pomace extract. The clinical study showed that the daily consumption of 1 g of aqueous extract of tomato pomace for 5 days exerted an inhibitory activity on platelet aggregation.