The Spain international, 32, lost his starting berth to Diego Lopez under Jose Mourinho last term but has been unable to win back his slot since Carlo Ancelotti took charge at the Santiago Bernabeu.
Casillas's struggles have prompted speculation he could seek a move away from los Blancos in an effort to maintain his position with la Roja ahead of next summer's World Cup.
Atleti, as well as Arsenal, have reportedly been monitoring his situation, but Simeone says Thibaut Courtois - who is on loan at the club for a third consecutive season - is his number one.
"Courtois is our goalie," he told reporters. "We also have two other goalkeepers waiting for their chance. So no, we wouldn't be interested in Iker Casillas."
Los Rojiblancos face Barcelona in the second leg of the Spanish Super Cup on Wednesday, which kicks off at 22:00 BST.