The underpants gnomes feature strongly in the South Park game the stick of truth. You enter the game as the new kid in town and have to fight your way through zombies, aliens, Nazi zombies, underpants gnomes and worse to recover the stick.
After attacking the school in order to rescue one of your allies your parents ground you and send you to bed where you are attacked by four underpants gnomes who shrink you. When you win the fight they escape down a mouse hold into with you have to chase them through the mouse hole and into your parents’ bedroom (I won’t say what the parents are doing as this is a family web site). You fight the gnomes again and after the final fight with the underpants warlock who eventually gives up and hands you a potion that will make you shrink or grow whenever you want.