At first glance, the interior of the church is unadorned: the columns between one chapel and another, the succession of arches, the cornice that runs throughout, all creates a bare, grand architecture. Everything converges on the altar, the architectural and spiritual center of the church.

At first glance, the interior of the church is unadorned: the columns between one chapel and another, the succession of arches, the cornice that runs throughout, all creates a bare, grand architecture. Everything converges on the altar, the architectural and spiritual center of the church.

The Latin cross plan of the church exhibits a wide central nave flanked by a series of five side chapels, each of them closed off by a marble balustrade and raised by three steps from the nave level. The church ends with the deep body of the presbytery divided into two parts from the main altar, behind which the friars'  choir is located. In the two rear walls from the end of the transept, two side entrances are found: the left one leads to the sacristy and cloisters, the right one leads to Campo San Francesco.

The interior measurements of the church take inspiration from Father Francesco Giorgi (1460-1540), ideas linked to cabalistic theories: the measurements of a church must be guided by the work of Divine wisdom as expressed in creation and in particular in the human body, the masterpiece of creation reaching ultimate perfection in Jesus Christ. Giorgi states that the starting point of perfection is the number 3, because it comprises itself three times, and that perfection is completed by the number 27, because it contains three times three, multiplied by itself (3x3x3=27): see De Harmonia Mundi totius cantica tria (Venice, 1525).

The central nave represents Jesus Christ, absolute human perfection towards God, and Father Giorgi utilizes 27 Venetian feet (43.20 meters). The cross of the nave meanwhile symbolizes Christ on the cross: as divinity is represented by number three and humanity by number two; the length therefore comprises six Venetian feet (9.60 meters).

The presbytery is a place of worship: to manifest the unity of God and the Trinity of the Persons Father Giorgi used number three added three times (to represent the equality of the three persons of the Trinity); the presbytery is subsequently nine Venetian feet long (13.40 meters).

The choir is devoted especially to the prayer of the clergy; they are united in prayer with the Nine Choirs of Angels; therefore the choir is nine Venetian feet long (13.40 meters).

Christians, who form the mystical body of Christ, the church, are not perfect; they are sanctified by the three persons of the Trinity (3x3). Imperfect mankind (represented by number two) cooperates, but it remains limited. The result is: 3x3=9; 9x2=18. The church is in fact 18 Venetian feet wide (28.80 meters).

In this world, mankind knows God with his reason, an imperfect means. Father Giorgi conveys this fact by applying number 9 to God and number 2 to mankind. Using this logic, the height of the church corresponds to (9x2), or 18 Venetian feet (28.60 meters).

The chapels of the central body of the church are 12 in number because the Church is founded on Christ (central nave) but grows and matures with the 12 Apostles.