Changes undergone by tomato-antioxidants during gastrointestinal digestion of raw and fried tomato, with or without presence of the probiotic Lactobacillus reuteri ATCC 55730, were studied. Frying process enhanced the extractability of antioxidant compounds, being their content higher in fried than in raw tomato. In vitro digestion led to a significant loss of antioxidant activity (65 and 75% losses for raw and fried tomato, respectively), and total lycopene (60 and 50% losses for raw and fried tomato, respectively); and promoted trans-cis lycopene isomerization initiated during frying. Bioaccessibility of the antioxidant compounds was within 10% and 30%, being higher for phenolic compounds in raw tomato but lower for total lycopene. Finally, although the presence of Lactobacillus reuteri ATCC 55730 reduced the bioaccessibility of antioxidant compounds, the results suggests that the tomato's antioxidant compounds could have a protective effect against the loss of viability of the probiotic.