This palace was built by Giulio Parigi, an architect who worked on the Pitti Palace for the Medici family, and who repeated the mediaeval leitmotiv of the projecting consoles that can be seen on the buildings beside it, between the ground and the first floors. The huge rectangular space of Piazza Santa Croce, created in front of the Franciscan Basilica, is the result of a 13th-14th century urban project whose mediaeval origins can still be clearly seen in many of the buildings surrounding its perimeter. However the two most famous palaces in the square actually date from a later period: Palazzo Cocchi-Serristori, which is an original adaptation of a 14th century house carried out by Baccio d'Agnolo towards the end of the 15th century (opposite the church), and Palazzo dell'Antella, which previously belonged to the Cerchi family (civic number 21-23), the leaders of the "White" Guelph party.

Palazzo Antella's lovely facade also stands out from the other buildings because of its murals: the festoons and grottesque figures were frescoed in 1620 in only twenty days by a group of twelve painters under the direction of Giovanni da San Giovanni, a friend of Niccolò dell'Antella.