"When you work as a humanitarian, you are conscious that politics have to be considered. Because if you really want to make an extreme change, then you have a responsibility," Jolie told Vanity Fair's contributing editor Janine di Giovanni.
"I honestly don't know in what role I would be more useful. I am conscious of what I do for a living."
When asked whether she would ever consider pursuing a life in politics, diplomacy or public service, Jolie responded, "I am open."
Earlier in the year, however, Jolie seemed uncertain on the topic.
In an interview with Good Morning America in May, when asked if she would try her luck in politics, Jolie had said, "If I thought I'd be effective, I would. But I'm not sure if I would ever be taken seriously in that way and be able to be effective."
She has travelled the world supporting several political and humanitarian causes, and made headlines in 2007 when she penned an op-ed for The Washington Post calling for global attention to end the genocide in Darfur.
She was recently presented with the honorary dame title by her Majesty Queen Elizabeth II for her efforts in fighting sexual violence.
The Academy award-winning actress is currently busy directing her self-written movie By the Sea in Malta.
The actress will be starring in the film alongside husband Brad Pitt for the first time since the couple shared screen space in Mr and Mrs Smith in 2005.