Samantha Morton previously played Mary Queen of Scots in Elizabeth the Golden Age and now she plays her mother in law.
Enzo Cilenti(Ruggieri), Amrita Acharia(Aabis), Danny Kirrane(Louis de Bourbon) all appeared in Il trono di spade (2011) as Yezzan zo Qaggaz, Irri and a Stark Soldier respectively, albeit in different seasons. Of course as Tywin Lannister, Charles Dance(Pope Clement) did appear in some of their episodes but none ever shared scenes with him.
Samantha Morton(Catherine de Medici) and Nicholas Burns(Antoine de Bourbon) starred together in Harlots (2017) before. Burns also acted with his on screen son Angus Imrie(Henry of Navarre) previously in Emma. (2020).
Both Navid Negahban(Claude de Guise) and Beth Goddard(Antoinette Guise) are only 6 years older than their onscreen elder son the Duke(Raza Jaffrey) and 10 years older than the younger Cardinal(Ray Panthaki) in real life.