Guani became the first Delegate of Uruguay to the League of Nations and was subsequently elected by his peers to the presidency of the Council Assembly in 1927.
Earlier in 1920 when the nations of the world met at the San Remo Conference, the Uruguayan representative, Dr. Alberto Guani, expressed himself in favor of Jewish aspirations in Palestine and fervently supported the Balfour Declaration of November 2, 1917, milestone fundamental in the creation of the Israeli state.
Guani entered the diplomatic service, and served as Uruguay's Plenipotentiary Minister in Austria-Hungary and Switzerland (1911), in Belgium and the Netherlands (1913), in France (1925–1926), and in the United Kingdom (1936–1938).
As Chancellor of the Republic of Uruguay during the presidency of Alfredo Baldomir, Guani was instrumental in the diplomatic battle that arose with the German battleship Graf Spee.
In the November 1942 elections, Guani was selected as the running-mate of Juan José de Amézaga when they won the primary of the Colorado Party.