Primary Antagonists are the main villains of the series. In each season there is usually a main antagonist, who is the center cause of the trouble. And a secondary antagonist, who causes trouble, but not as regularly or big.
- Main Villain(s): Jenny Humphrey and William van der Woodsen
- Secondary Villain(s): Tripp van der Bilt and Maureen van der Bilt
- Main Villain(s): Juliet Sharp and Russell Thorpe
- Secondary Villain(s): Damien Dalgaard and Vanessa Abrams
- Main Villain(s): Tripp van der Bilt, Louis Grimaldi and Diana Payne
- Secondary Villain(s): Ivy Dickens