Bryan Cranston, Jessica Biel, Adam Scott and Christina Applegate also appear in the Jimmy Kimmel Live! segment which aired earlier this month.
In the video, Cowell is called a "d**k", while Modern Family's Eric Stonestreet is accused of being "awkward and yelly".
Cranston wraps up the feature when he is told to "lose some weight Heisenberg". The actor responds by adopting his Breaking Bad persona and threatening the Twitter user.
Previous instalments of the segment have included Zooey Deschanel, Kristen Stewart, Katy Perry and Justin Bieber, as well as Joel McHale, Louis CK, Anna Faris and Kristen Bell.