The interior, mainly in Gothic style, has an single nave in a Latin cross shape, supported by ten big ogival traverse arches. The church is rich with paintings made by artists from Gubbio of the 16th century (Nucci, Basili) but also some from further away (Sinibaldi Ibi, Giuliano Presutti, Dono Doni).

There is a very significant Baroque chapel that opens up in the middle of the right wall: it contains frescoes by Allegrini and a canvas (the Birth of the Virgin) by Gherardi.
To the left of the main altar there is the Seat of Magistrates, with false inlays by Benedetto Nucci. The choir hosts the Episcopal seat, carved at around the middle of 16th century. The late antique sarcophagus below the major altar contains the relics of St. Giacomo and Mariano, titulars of the Church. The walls still bear traces of frescoes from the 14th and 15th centuries. The wall paintings of the apse, of the triumphal arch and of the left-side chapels are artworks by Augusto Stoppoloni (1916-18).
Source: http://gubbio.infoaltaumbria.it