She governed the Republic of Florence during the absences of her son, Lorenzo II de' Medici, in the period of 1515–1519.

She helped restore the Medicis to power after they had been exiled, worked to secure a French royal marriage for her son, and was also influential at the court of Pope Leo X, her brother-in-law.

[4] In 1486, Orsini's marriage to Piero di Lorenzo de' Medici was arranged by his uncle, Bernardo Rucellai who stood in as proxy.

[5] In February 1488, she brought a dowry of 12000 ducats when she joined her husband at a wedding in Rome attended by Ferdinand and his wife Joanna of Aragon.

[8] The renovation included expanding dormitories for the Dominican sisters, rebuilding the church, and adding other rooms and chapels.

[10] Under Florentine law, women and children were not included with their husbands or fathers in exile, though their funds and ability to travel were limited.

[19] Alfonsina returned briefly to Florence in 1507 to attempt to claim her dowry and to seek a husband for her daughter, Clarice.

[26] When her brother-in-law was elected as Pope Leo X, she took advantage of the situation to increase her income and provide additional funds to her son.

[30] Alfonsina was working so that her son would have sole authority in Florence, while others, led by Lucrezia, wanted a more distributed government.

[36] When Lorenzo took the Florentine army in the summer of 1515 to support Pope Leo and the Spanish in the war against Francis I of France, Alfonsina took up the rule in his name.

[42] When the Swiss mercenaries left the Spanish army, she began sending treaty proposals to Francis.

[45] She had the responsibility of planning the official visit of Pope Leo to Florence in November 1515 as he was traveling to sign the peace treaty.

[47] While he was away again starting that fall, she ruled remotely from Rome, providing direction to Goro Gheri who worked in Florence for her through 1517.

[50] Her rule was not popular, and even during Pope Leo's visit in 1515, posters went up protesting her greed and naming her an enemy of liberty.

[53] Until her husband's exile, she sponsored the work of Mariotto Albertinelli, sending his paintings to her extended family throughout Italy.