*Android 21 is described as a tall, curvaceous scientist with glasses and long bushy auburn hair. She has a gold ring on her left middle finger, and black nails. She wears a pair of hoop earrings, a sleeveless, short blue and red checker pattern high-neck minidress with opaque black tights, matching black detached arm sleeves, and blue (left foot) and red (right foot) ankle heel boots with gold tips. She also usually wears a white lab coat with her outfit. Her eyes are similar to that of Dr. Gero's Androids, such as Android 18.

In her true form, Android 21 keeps her curvy body, her skin turns pink, her hair becomes white with a pink tint, her ears become pointed, her eyes changing depending on if her evil half takes over, and she gains a tail. Her attire changes to a black tube top, keeping the black arm sleeves with gold bracelets at the ends, her boots become black, and also gaining white baggy pants. It's noted that she most resembles a Majin in this form. Her eyes slightly vary depending on which moral alignment she represents. In her good representation, she retains the eyes from her human form. In her evil representation, her eyes instead are more similar overall to that of a Majin.

Due to her biology, Android 21 has a natural, compulsive instinct to feed (which grew out of control due to cells in her body going berserk). Like Majin Buu, she prefers sweets and confectioneries, her favorite being macarons. However, she has no control over her hunger and constantly fights to keep herself from turning others into treats and devouring them.

Her hunger is so great and painful that it has led to Android 21's psyche being damaged and manifesting a split personality. The longer she goes without feeding, the more the evil side of her gains control. When her true persona is in control she acts like a kind and motherly woman who was concerned about Android 18 and agreed to help her. When her evil persona is in control, however, she becomes a sadistic and power-hungry sociopath, wanting to "devour" all the powerful fighters, drawing to the point of near insanity. Her gluttonous lust for "devouring" powerful fighters is similar to the traits of the Majins, inherited when Buu's cells were added to her. Her good side is friendly towards Good Buu presumably due to their shared biology and love of sweets.

Her personalities were later transferred to her two halves after her good self-managed to use fission as a result of the emotional turmoil caused by the death of her adoptive son, Android 16, who was killed by her evil side as a result of her losing control.

Though Android 21's good side is aware of the fact that her human template was the mother of Android 16's template, which causes her to develop mother-like affection for him, she admits she has little to no memory of her former life as a human, though she enjoys thinking about what her template's name and life might have been like. She is also apparently unaware that Dr. Gero was the father of Android 16's template or of his relationship with her human template. During one of her conversations with the player, she notes that her creator, while not a good person, was a brilliant scientist and admits she would like to know the reason she was created though admits that he might not answer her questions or that if he did that she might not want to know the truth. Interestingly, she never mentions Dr. Gero's name directly, though it is obvious he is the one she is referring to. Presumably, her knowledge of him either comes from what little memories she possesses and what she has been able to learn through research of herself and Android 16.

In contrast, her evil side cares nothing for Android 16 and believes that Androids have no use for things like family and loved ones as she orders Android 18 to attack her husband Krillin. Additionally, she only values Dr. Gero for his labs and research.*