The McPoyles are a family of that have developed a hatred towards the Gang. Brothers Ryan and Liam went to elementary school with Charlie and Mac. Their mute sister Margaret is often present when they annoy the Gang.
It is strongly implied that the two brothers Ryan and Liam have an incestuous relationship with each other and with their deaf mute sister. Liam seems to have a sexual attraction for Dennis as well. ("The Gang Gets Held Hostage") The McPoyles also have a strange obsession with milk.
They have numerous other siblings and family members (all noticeable from their unmistakable features such as unibrow, acne and eczema) numbering around 14. Their brother Doyle McPoyle is an aspiring football player. ("The Gang Gets Invincible") Their sister, Margaret is a deaf-mute.
They are enemies with Charlie for foiling their plan to become rich through a false molestation lawsuit against the school district ("Charlie Got Molested"), and with the rest of The Gang for ruining Doyle's chance to play for the Philadelphia Eagles when Frank accidentally shoots him in the leg. ("The Gang Gets Invincible")
When Liam becomes engaged to Maureen Ponderosa, it greatly disturbs Ryan and the other members of the McPoyle family, because, as Ryan says, the bloodline has been "pure and clean for a thousand years", which he clarifies means that no McPoyle has "bred outside of the bloodline" (Dee is not surprised at all by this). Later, though, Liam reveals that his motive for marrying Maureen is to taint the bloodlines of the rest of the world, allowing the McPoyles to take over the world. ("The Maureen Ponderosa Wedding Massacre")