O'Neill's men will face Poland in their Group C opener at the Allianz Riviera in Nice on June 12 before taking on Ukraine in Lyon and world champions Germany at Parc des Princes in Paris.
Lewandowski was on target 13 times for Poland in qualification, while Germany's Muller found the net on eight occasions.
O'Neill told BBC Sport: "Both showed what they're capable of qualification. In many ways it's a good test for us, we have three Premier League centre-backs in our squad, it's a good challenge to go against Muller and Lewandowski.
"There's a lot of positives we take into this tournament, we've always done better against the bigger nations [in his tenure], we go into this tournament with everything to gain.
"Having watched tournament football, the most important thing is to try and take something from your first game because then you're up against it.
"The fixtures work in our favour because we have to play Poland and Ukraine before Germany.
"Come June we'll definitely be ready to play. It's a perfect opportunity for us. Everyone's looking forward to it."