Leverkusen have stormed to a first-ever Bundesliga title and are on course for a remarkable treble without tasting defeat in 51 games so far this season.
Atalanta have also had a memorable campaign as they have reached their first-ever European final, qualified for next season's Champions League and narrowly lost the Coppa Italia final to Juventus last week.
"They've had a perfect season until now. I don't want to say they have any shortcomings but every team is beatable," De Roon, who will miss the match due to injury, said on Tuesday.
"They seem invincible but maybe we can change things."
Under the tutelage of Gian Piero Gasperini, Atalanta have risen from a provincial club in the shadows of nearby giants AC Milan and Inter Milan into regulars in European competition.
However, they have so far failed to end a 61-year wait to win a trophy.
"All that matters is that we want to win the game. With or without me, it doesn't matter, what matters is lifting the trophy," added De Roon.
"We will do everything in our power to do that."
Leverkusen boss Xabi Alonso has turned down the advances of former clubs Liverpool and Bayern Munich to commit to the German champions next season.
Gasperini hailed the loyalty shown by the Spaniard to stay put with the club that offered him his first senior coaching role.
"What Xabi Alonso has done is wonderful because with the performances this season, he had the opportunity to go to a number of big clubs," he said.
"But he thought the club (Leverkusen) believed in me when I was not so well thought of."
Atalanta have enjoyed two of their greatest-ever European nights on the road to Dublin, knocking out Liverpool in the quarter-finals and Marseille in the last four.
Gasperini is hopeful those feats will fill his players with confidence to end Leverkusen's incredible run.
"We are aware that we are facing a great team. We know that they are undefeated and we know that they have had an amazing season," said the 66-year-old.
"Our journey, however, was also very good as we beat very strong teams to reach the final. We also have belief."
