The main window replaced a mullioned window with mosaic decoration in the 13th century of which there are still visible traces above the portal.
The interior is divided into three naves by pillars, with side chapels.
On the walls you can see frescoes dating from the 13th to the end of the 16th century. Of particular significance, on the second pillar on the right is a Crucifixion attributed to Maestro della Dormitio, to whom the decorations of Saints which run vertically on the adjoining walls can also be accredited. At the bottom of the left-hand nave, the fresco Virgin and child with Saints Dominic and Thomas from the school of Pier Matteo d'Amelia from the end of the 15th century is particularly noteworthy.
Leaning against the pilaster of the triumphal arch was an exquisite Renaissance marble tabernacle from the school of Agostino di Duccio, which can today be found in the Pinacoteca Civica.
On the left, in the large cappella del Rosario (Rosary Chapel), frescoed in the second half of the fifteenth century by Flemish artists with stories from Genesis, are paleontological and archaeological finds from the Late Pleistocene, unearthed in the local area.
In the underground area of San Domenico there is also a small proto-Romanesque church with a single nave which has traces of frescoes datable between the 12th and 14th centuries.