The main streets of Ortygia are lined with charming palaces. On Corso Matteotti, whose buildings are built in fascist style, lies the medieval Greek Palace (now the INDA Palace, National Institute of Ancient Drama) which, although remodeled, retains fourteenth century structures, visible in the mullioned window with two lights, in the lodge and in the staircase. At the end of the Corso is located Piazza Archimede, a nineteenth-century charming square.

In the center of the square there is a beautiful fountain representing Artemis, her nymphs and sea monsters. It is also possible to admire a few buildings from different eras: the eighteenth century Palazzo Pupillo Bucceri Lanza, where now the museum Arkimedeion is located.

On the Via della Maestranza, the main street (and oldest) of the island of Ortigia, were built mansions, often baroque, including: Palazzo Interlandi Pizzuti, Palazzo Impellizzeri, Palazzo Bonanno, Palazzo Romeo Bufardeci, Palazzo Rizza.

In the district "spirduta" of Ortigia, one of the most interesting buildings is the Palazzo Mergulese-Montalto, whose construction dates back historically to the fourteenth century, built in late Gothic style in 1397 by the noble lady Macciotta Mergulese, but then donated in the fifteenth century to the powerful family of Syracuse Montalto by Queen Isabella of Aragon.

In Piazza Duomo is located Palazzo Vermexio (the name comes from Giovanni Vermexio, the architect who designed it and built it in 1629), also known as the "Palace of the Senate", the town hall of the city of Syracuse. It was built on the ruins of the first and unfinished Ionic temple next to Palazzo Salonia-Interlandi and opposite Palazzo Beneventano del Bosco, which was built just after the earthquake of 1693.

The square has a semi-elliptical shape and is dominated by the imposing facades of these palaces, of the Baroque Cathedral (Duomo) and of the abbey church of Saint Lucia. Piazza Duomo is strongly suggestive, and is considered among the most beautiful squares in Italy.