The first season of the upcoming movie is based on Jeffrey Toobin's best-selling book "The Run of His Life: The People v. O.J. Simpson", said The Hollywood Reporter.
Handler, 54, will play attorney Alan Dershowitz, another member of Simpson's "Dream Team" legal defence.
Ladd, 63, meanwhile, will portray Linell Shapiro, the wife of Simpson's defense attorney Robert Shapiro.
The cast also includes Malcolm-Jamal Warner, Selma Blair, Jordana Brewster and Cuba Gooding Jr as OJ Simpson.
The FX series is created by "American Horror Story's" Ryan Murphy and Brad Falchuk.
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