* Barbara Reynolds (Anne Archer) — Frank's gold-digging ex-wife, Dennis and Dee's mother. She was a cold, cruel, selfish woman with little affection for her family. Frank referred to her as his "whore wife". The finale of season two revealed that Barbara tricked Frank into raising the twins because she thought he was wealthier than their biological father, Bruce Mathis (played by Stephen Collins). She died of a botched neck-lift in the third season; Frank, ecstatic over the news, delivers the news to The Gang armed with champagne.
* Bruce Mathis (Stephen Collins) — Dennis and Dee's biological father. The antithesis of Frank Reynolds, Bruce devotes his time and money to charities and philanthropic efforts, including adopting several suffering children in Africa. He reconnects with his twins through Sweet Dee's MySpace page (in the episode "Dennis and Dee Get a New Dad"), but they are unable to have a successful relationship with him because of his good nature. He returns in "Dennis and Dee's Mom Is Dead", in which he inherits Barbara's fortune and calls The Gang "the most horrible people alive".
* Bonnie Kelly (Lynne Marie Stewart) — Charlie's mom, a sweet and timid woman who is attracted to cruel men, but not to Dennis. She had a one-night stand with Frank Reynolds 30 years ago, possibly making him Charlie's biological father. She later reconnects with Frank, enjoying his harsh treatment and becoming his "bang-maid", but she quickly transfers her affections to the intimidating Luther Mac after meeting him at a dinner party thrown by Mac and Charlie. Quite neurotic and emotional, she is prone to dramatic episodes. There is evidence (as shown in the Christmas special) that Bonnie may have once been a prostitute, a fact which greatly upsets Charlie. In "Mac's Mom Burns Her House Down", Mrs. Mac accidentally burns her house down and goes on to move in with Bonnie, the two bonding over mutual racism.
* Luther McDonald (Gregory Scott Cummins) — Mac's father, a convicted felon. He is tall and has numerous tattoos and a generally intimidating appearance because he never blinks. Possibly due to his past imprisonment and intimidating presence, he is one of the few people The Gang does not immediately try to manipulate or exploit. The warm and gentle Bonnie Kelly is attracted to Luther's aloof behavior and criminal past. In his first appearance ("Dennis and Dee Get a New Dad"), he attempts to get Mac and Charlie (who have come to visit him in prison and bond with him) to smuggle heroin into the prison through mac and charlies anus. In "Dennis Looks Like a Registered Sex Offender", he is out on parole and convinces Mac to help him "take care of some people" he has listed, including former witnesses in his trial and the judge who sentenced him. Charlie and Mac become convinced that he is using them as drivers while his murdering the people on his list (similar to the movie Collateral) and try to sabotage Luther's parole. They fail to do so and Mac is initially relieved when Luther is arrested for violating the parole on his own. However, Mac is horrified to learn about the parole violation because Luther was apologizing to the people on his list and didn't harm any of them and the parole violation occurred when Luther made proscribed plane reservations to leave the state and take Mac and Charlie to the Baseball Hall of Fame. Luther calmly tells Mac he had no plans to hurt him before, but once he gets out of prison again, he's definitely going to murder him and Charlie. When he is paroled anew, Mac and Charlie fake their deaths to escape what they believe is an unstoppable wrath. Luther forgives Mac for this in a note which also tells Mac to stay far away from him and that he loves him and always had. He now spends his days sunning on a Mexican beach.
* Mrs. McDonald (Sandy Martin) — Mac's mom first appears in "Mac Bangs Dennis' Mom". Like Bonnie, she thinks Dennis is unattractive. She is usually seen smoking and watching television on the front porch of her home. She is extremely apathetic, demonstrated by her falling asleep at her son's "funeral" with a portable TV on her lap and remaining the same as usual when Luther is out on parole, and she often communicates with minimal words and unenthused grunts, (which Mac serves as translator for). In "Mac's Mom Burns Her House Down", she accidentally burns her house down and goes on to move in with Mrs. Kelly, the two bonding over mutual racism.
* Pop Pop (Tom Bower): "The Gang Finds a Dead Guy" found Dennis and Dee's grandfather languishing in a nursing home, rarely visited by relatives. He was a former Nazi of whom Dennis is the spitting image. Charlie pretended to be Pop Pop's grandson when he and Dee visited him; after Pop Pop's death, Charlie appropriated Pop Pop's Nazi-uniform cap. It is not stated whether Pop Pop is Dennis and Dee's paternal grandfather or maternal grandfather. It's more likely that he is their maternal grandfather, for it is seen in a picture of his young self that he bares a striking resmblince to Dennis.