Piero Guicciardini was born in Florence in 1560 and at an early age undertook a career in diplomacy which brought him in 1587 to Naples, Sicily and Malta to announce Grand Duke Francesco I's (1549-1609) death, and in 1609 to the Court of France to give tidings of the death of Grand Duke Ferdinando I (1549-1609). In April of 1611 he was appointed ambassador to Rome, taking the place of Giovanni Niccolini (1544-1611).

In the two trips Galileo took to Rome, in 1611 and in 1615, Guicciardini hosted him at the Tuscan Embassy. Much of what we know about Galileo's trip to Rome in 1615 is gathered from the reports Guicciardini sent to the Secretary of State Curzio Picchena (1553-1626), in which he took every opportunity to signal the dangers Galileo was risking. Making use of his connections in Roman political circles, Guicciardini, in May of 1616, after the condemnation of the Copernican system, hastened Galileo's return to Tuscany.

Guicciardini remained in Rome until 1621. Two years after his return to Florence he was appointed Grand Majordomo. He died on September 13, 1526.