John Lambros made the prediction during a heartfelt speech at the couple's wedding ceremony, reported People magazine.
Given their common passion for human rights causes, Lambros said, "Okay, I am projecting, but I am also making that call public tonight... Perhaps the first husband-and-wife team to win the (Nobel) Prize for Peace."
Lambros joined three others in delivering speeches during the ceremony. Clooney, 53, and Alamuddin, 36, got married in Venice, Italy on September 27.