Milady is initially an antagonist due to her work as an agent for the Cardinal. Later in the novel, she is revealed as a full-fledged antagonist in her own right, perhaps even more dangerous than the Cardinal himself. We learn that she once broke Athos’s heart, attempted twice to murder D’Artagnan, succeeded in murdering Constance Bonacieux, and convinced John Felton to assassinate the Duke of Buckingham. We further learn that she once seduced a certain priest who fled with her, stole for her, faked being her brother, and eventually committed suicide. Her powers of destruction in The Three Musketeers are incredible, and there are some not-so-veiled allusions to her being a deadly siren (refer to the Character Analysis for more on this).
D’Artagnan’s status as a royalist automatically makes the Cardinal his enemy. Although the Cardinal is the King’s most trusted adviser and in practice France’s real head honcho, the two of them definitely have a certain competition going on. The Cardinal in particular wants to destabilize the King’s marriage, since the Queen once rejected him. To these ends, the Cardinal keeps careful tabs on the Queen and hopes to expose her love affair with Buckingham as fast as possible. He also wants to win the war against France, again, motivated by his past love for the Queen. These two desires instigate the two major story lines in the book – recovery of the diamond studs and the race to prevent Buckingham’s assassination. The Cardinal might thus be considered the chief antagonist of the novel in the sense that he pulls the biggest levers. Unlike Milady, however, the Cardinal is not shown to be an inherently evil person. He respects D’Artagnan and his friends and eventually spares D’Artagnan’s life and offers him a promotion. He and the four friends seem well on their way to a good relationship by the end of the novel.