Spiropulu served as Chair of the Fermilab Physics Advisory Committee, member of the High Energy Physics Advisory Panel to the U.S. Department of Energy and the National Science Foundation, chair of the Forum of International Physics and member of the Physics Policy Committee of the American Physical Society and Chair of the Caltech Faculty Board. She is a member of the Aspen Center for Physics and serves on the Advisory Panel of the HEP Forum for Computational Excellence. She testified in Congress in May 2017 on the Department of Energy's High Energy Physics Program Funding for FY 2018 and was selected to participate in the 2020-2021 Defense Science Study Group of the Institute for Defense Analyses (IDA) sponsored by DARPA. She is the founder of the Physics of the Universe Summit that explores challenges in emerging and cross-cutting areas of science and technology. Spiropulu participated at the White House Summit on Advancing American Leadership in Quantum Information Science, on September 24, 2018 and participated in the signing ceremony for an International Cooperation Agreement between the U.S. Department of Energy, the National Science Foundation, and CERN in May 2015.