As quoted from Bill Watterson:

"As a few readers guessed, Miss Wormwood is named after the apprentice devil in C.S. Lewis' "The Screwtape Letters." I have a lot of sympathy for Miss Wormwood. We see hints that she's waiting to retire, that she smokes too much, and that she takes a lot of medication. I think she seriously believes in the value of education, so needless to say, she's an unhappy person."

As quoted from Me:

Mrs. Wormwood is the destroyer of dreams and presenter of knowledge. Pertaining to this statement, she is always involoved in Calvin's daydreams as an alien or monster trying to imprison him. But she is also forced to put up with Calvin's constant "Show and Tell" lectures where he says that one day all these jerks in his class will be left behind or something to that effect. He always tries to point out the injustification in school and the fact that his punishments are unfair and have no reason to be handed out.