An activist and supporter of various charities, Dern advocated for Down syndrome awareness in a cover story for "Ability Magazine". In 2018, Dern brought activist Mónica Ramírez to the 75th Golden Globe Awards as a guest. In the same year, she attended a Families Belong Together event and expressed her support for immigrants' rights. She is also an advocate for women's rights, gender pay parity, as well as combating gun violence and climate change. In 2019, she became a board member of the Academy Museum of Motion Pictures.