I think the easiest way to answer this question is to consider his behavior and his attitude in the face of being physically and intellectually so different from his peers. Consider how he reacts, in the opening scene of the movie, when the kids are passing him around the Sunday School classroom over their heads (an activity which happens frequently). Sure, he's demanding they put him down, but when he is at last released, what does he do? Does he lash out? Does he seek retalliation? Does he cry or really even complain? All of these responses would be almost expected from a twelve year old after being teased and physically man-handled by a class full of bigger (but not older) kids. Simon just sort of accepts it. Clearly, he doesn't like it, but it does not rattle him or cause him to feel insecure or inferior. In fact, you could almost argue it has the opposite effect. Simon treats his differences (size, voice, intelligence, lack of parental support) as fuel for his sense of confidence that God has a plan for his life, which lends him high self-esteem.
Another clear example of Simon's self-esteem comes in the baseball scene. Every single game, it is obvious, Simon is used with the expectation that the pitcher will simply walk him, because his strike zone is so small. Again, he accepts this role as part of his purpose and identity. He grumbles a little bit, but really never fights back, until the day he hits the foul ball which kills his best friend's mother. Even in the face of what is essentially accidental manslaughter, Simon's sense of maturity permeates everything. An event like this, for almost anyone, would be devastating and likely permanently scaring. Yet, Simon's already keen sense of self, faith, and knowledge that he has a purpose in life, causes him to get through this tragedy and to bring his best friend with him. Almost everything in Simon's character points to a high sense of self-esteem.