The interior of San Nicolò is composed by a single axis with two chapels; the walls feature an order of pilasters framing arches, surmounted by an attic window. The gray basalt stone and the plaster are in Tuscan style, characteristic of Brunelleschi's works. The windows have carved framed internally, and the outer walls that are rustic. The great arch before the choir is inspired by Bramante. In the chapel of SS. Sacramento, on the right, is a precious triptych by Giovanni di Paolo, Siena (1440) of the Madonna, St. Nicholas and another saint.
The body of San Longino, patron saint of the town, rests under the altar. The paneled ceiling was restored by Paolo Zampi, engineer of Orvieto, in the early 1900s; it was previously covered with a large canvas painted with the Virgin and Angels above a large cloud and St. Nicholas below it. In 1700 a beautiful organ was placed above the central door.
The architect Renato Bonelli, Orvieto praised the façade: "... harmony in the lower zone; purity of lines, composition and purity of design: a façade design that slowly fades at the top in a different form. Below the entablature runs straight... has only one projection corner, but above the entablature is broken several times at the secondary and upper pediment pilasters. So the façade as it marches upwards frays, divides, it has variations that contribute to give her momentum. Doors have an air of Florence, they seem drawn from a Tuscan. "