Moe is characterized by a short, violent temper (particularly aiming a makeshift shotgun at customers), a somewhat low self esteem coupled with homicidal and suicidal tendencies and a proclivity towards obsessive behaviors. He has an annual Christmas tradition of attempted suicide, but his attempts are comically unsuccessful (landing on a hot-air balloon after jumping out of a plane, for example). He has called the suicide hotline so many times that they have blocked his number. Although he has a violent temper and homicidal tendencies, there were instances where even he did not approve of violent depictions. This was most especially evident when he saw the Mel Gibson-starring remake Mr. Smith Goes to Washington, where he flatly said "Well, that was disgusting!" while leaving the theater with the rest of the sickened audience regarding the infamous killing spree ending.

Moe is especially bitter, keeping an enemies list nearly identical to that of Richard Nixon, with the addition of Barney (the latter simply because he pointed out that it was plagiarized from Nixon's list). He has assumed a leading role in many of Springfield's angry mobs (including, at times, starting mob riots for the sake of doing so), and kidnapping Talking Heads vocalist David Byrne. He has also engaged in bizarre behavior, such as shooting at Carl, robbing Homer of expensive pants, keeping Hans Moleman under his bars in a subterranean torture chamber, perpetrating insurance fraud, and stalking various townspeople. This behavior is further exhibited when he becomes the self-proclaimed Emperor of Springfield when the town is trapped in a dome.[8] His leadership is challenged by Barney who throws a Molotov Cocktail at him, which Moe successfully throws back. He once implies that he probably wouldn't continue to be suicidal if Reverend Lovejoy had told him that he had much to live for.

He also was shown to be notoriously cheap to his customers, as he drove away designated drivers from his bar on Saint Patrick's Day claiming he has "no time for cheapskates" due to it being the biggest drinking day of the year, and once told Homer when giving him a beer while the latter was awaiting quadruple heart surgery that it wasn't a free beer. In fact, one of the few times he DID give anyone, let alone Homer, a free beer, was when he was intimidated by Homer's Zorro-esque actions regarding challenging someone to a duel after thwarting an attack at a movie theater he saw a Zorro film at.

Moe has a strained love life due to his vulgar attitude, especially towards women. Nevertheless, Moe has had a number of romantic experiences, including sleeping with his waitress Colette[10], dating a woman named Renee, and enjoying the company of many women after he had plastic surgery to correct his ugly appearance. According to "The Fight Before Christmas", Moe was in a relationship with singer/songwriter Katy Perry as she was 'into puppets'.

He has long been infatuated with Homer's wife Marge (whom he often refers to as Midge) and has on occasion professed his love for her and tried to win her away from Homer. His infatuation with Marge was intense enough to enter stalker territory, where he apparently bugged the Simpsons home to overhear Marge (unaware that he himself was being monitored by the FBI for this, which according to them, each of his statements would "add another year to the slammer" (presumably referring to what Moe's prison sentence length would be if he were to be caught and brought to charge for it).