Guillaume has been serving on the Committee on Civil Liberties, Justice and Home Affairs (LIBE) since 2009, where she is in charge of human rights.

[6] Between January 2012 and 2014, Guillaume served as Vice President of the Progressive Alliance of Socialists and Democrats parliamentary group[7] in charge of Citizens' Europe, along with Véronique De Keyser, Enrique Guerrero Salom, Stephen Hughes, Rovana Plumb, Bernhard Rapkay, Libor Rouček, Patrizia Toia and Marita Ulvskog.

In this capacity, she was in charge of the parliament's transparency register and served as Vice Chairwoman of the Working Group on Information and Communication Policy.

In 2020, Guillaume joined Mounir Satouri, Frédérique Dumas and Hubert Julien-Laferrière in visiting several refugee camps in northern Syria that hold individuals displaced from the Islamic State of Iraq and the Levant, including al-Hawl and Roj.

[9] Ahead of the 2022 presidential elections, Guillaume publicly declared her support for Anne Hidalgo as the Socialists’ candidate and joined her campaign team as diplomatic adviser.