Mandy (mostly) has a morbid attitude and she is the main deuteragonist. However, unlike Billy, she is more stable, sane, and intelligent. She'll punch or otherwise injure (physically, emotionally, mentally, or any combination of the three) anyone who gets in her way. She is Billy's "best friend" regardless of the awful way she treats him. She is known for rarely smiling, the result of which made reality fall apart. She orders Grim and Billy to do chores for her, among a slough of other grunt work. She is naturally hostile and cynical, and is shown in one episode to have physical difficulty saying the word "please."
Billy and Mandy are best friends, although the true nature of their relationship is somewhat enigmatic. At first glance, Mandy appears to have a relationship with Billy much akin to a master and slave. They met when they were very young; Billy had stuck an ice cream cone on her face, for which she then punched him. She constantly berates and embarrasses him for his absurd ways. While she will often go entirely out of her way to save him whenever he is in danger, she will always have an excuse for it, convincingly that it's all for her own benefit. She has also allowed Billy to engage in physical contact with her on numerous occasions without reprimanding him; for example, he has licked her many times, also hugged her, and even kissed her. She fears Billy's deranged dark side, having herself acknowledged that Billy is dangerous when angered. While often cold and acerbic, she has also showed a possible soft spot for Billy.
Mandy uses and exploits Grim as her own personal supernatural slave. Often, she abuses his powers for her own selfish purposes. While she is distant and not on what could be considered friendly terms with the Reaper, it can be inferred that they share a cold connection to one another. Often, they agree with each other when it comes to more morbid topics, and seem to somewhat enjoy each others' company. Mandy originally became Grim's friend and master through a game of limbo, wherein she proposed that if he won, he would get Billy's pet hamster Mr. Snuggles and Billy; but if she won, he would be their best friend forever.