Giovanni Antonio was born in Florence on September 14, 1674, the only son of the Marquis Donato Guadagni and his wife Maddalena, née Corsini, sister of the future Pope Clement XII.
On the 3rd of May 1696, he graduated from the University of Pisa in both civil and canon law. He moved to Rome as a lawyer. Shortly afterwards he returned to Florence and following his religious vocation against the advice of his family, enterimg the Discalced Carmelites in Arezzo. On the first of November 1700, he made his solemn religious profession, taking the name of John Anthony of St. Bernard. He continued his studies in philosophy and theology in the monastery of the Order in Florence. In 1702 he received priestly ordination, was then appointed prior of the Florence monastery, then provincial for Etruria, where he founded a monastery in Pisa. In 1724, at the request of the Grand Duke of Tuscany, he was elected bishop of Arezzo. He received the consecration from the hands of his uncle, then cardinal in Rome, in the church of Santa Maria della Scala, on December 31st of that year.
On the 9th of March 1725, he made his solemn entry into Arezzo. In 1730 he celebrated a synod there, both to affirm some principles on the governance of the diocese and to make the clergy attentive to Jansenist errors..
In the conclave of 1730, his maternal uncle was elected Pope, taking the name of Clement XII. In his second consistory held on 24 September 1831, he created his nephew a cardinal. On October 14, he received the cardinal's hat in the cathedral of Arezzo with the presbyteral title of Saints Sylvester and Martin ai Monti. The following year he resigned from the office of bishop, to go to Rome where he was appointed Vicar for the diocese of Rome, a position he held until his death. In 1738 he became commendatory abbot of the abbey of Grottaferrata.
In 1750 he became cardinal bishop of Frascati. In 1756 he became sub-dean of the College of Cardinals and opted for the suburbicarian see of Porto and Santa Rufina.
He took part in both conclaves of his cardinalate, that of 1740 which at the death of his uncle saw the election of Benedict XIV; and that of 1758, with the election of Clement XIII.
He died in Rome on January 15th of the following year, in the odour of sanctity. The funeral was held in the Roman church of his Order, Santa Maria della Scala, where he was buried.
In 1763, the process for the cause of Beatification and Canonization was opened.