She was one of the four children of Prince Jean, Duke of Guise (1874–1940), who would become the Orleanist pretender to the French throne in 1926, and Princess Isabelle of Orléans.

While her father sought in vain to obtain permission from the French government to serve in the military, the rest of the family hastened back to Morocco.

[1] In 1923 the tradition of Orléans princesses marrying only other royalty (since the alleged 1681 wedding of La Grande Mademoiselle) was dispensed with, as nearly all of her relatives attended Isabelle's wedding at Amélie of Orléans château in Le Chesnay on 12 September to Count Bruno d'Harcourt (1899–1930), son of Count Eugène d'Harcourt and Armande de Pierre de Bernis.

[1] An automobile racer, Harcourt was killed during practice for the Moroccan Grand Prix, leaving his wife with four children:[1] As a widow, Isabelle remarried the Bonapartist Prince Pierre Murat (1900–1948) in 1934, at Jouy-en-Josas, "upon renunciation of the rank and prerogatives appertaining to princesses of the House of France".

In 1940, as World War II began and when her father died, Isabelle again took refuge at the family estate, Larache, in Morocco, where she shared quarters with her mother, and her elder sister the widowed Princess Françoise of Greece, along with her brother Henri, Count of Paris and the latter's son, Prince Michel d'Orléans.