The interior is overflowing Baroque, with statues by Jacobo Bertessi, and the vault was painted by Antonio Palomino to have it ready on Saint John's Day in 1701. Luis López, son of the painter Vicente López, carried out a restoration of the frescoes in 1861.

The main altarpiece is that of the missing church of Asunción de Betolaza (Álava), which was brought to the church of Santos Juanes in 1969.