Santo Domingo is the biggest and richest monastery in Antigua. The museum was founded in 1542, or the same year as the city was established. Construction began with the set of impressive monuments, including a large church (completed in 1666). The museum is full of colonial and contemporary art, archeology artifacts, handicrafts, and even a pharmacological museum.

Casa Popenoe is a private home open for public viewing. The house was built in 1636 for the Spanish judge Don Luis de las Infantas Mendoza. Today, the home illustrates wonderfully how wealthy people lived in the colonial era. The house was partly destroyed by an 18th century earthquake, but has since undergone a full scale restoration at the beginning of the 20th century.

Situated in the town center, Museum of Colonial Art is a fantastic piece of 16th and 17th century colonial art in regards to architecture. Inside, the building features a lovely collection of art, as Tomas de Merlo and Cristobal Villalpando are among the authors of the paintings located inside the exhibit.

The Jade Museum offers authentic Guatemalan jewelry. Conveniently situated in the city centre, the museum presents a great look at Mayan culture and Jade material that was used for centuries to decorate bodies, carpets, religious artifacts, homes, and churches.

Guatemala’s first printing press was established here in 1660. In 1956, the building became home to the Museum del Libro Antiguo. Among the exhibits, visitors will find a copy of the original printing press along with an overview of the history of printing, the will of Hermano Pedro - Guatemala’s most well known religious character - as well as a room dedicated to the process of making marbled paper.

The Museum of Santiago de los Caballeros is located in front of Central Park, at City Hall. The museum offers five exhibition rooms with ancient paintings and sculptures. In one of these rooms, tourists may observe a frame representing the old city, as well as witness other important changes to the city. Swords, cannons, and muskets are also exhibited here.

The Textile Museum (Museo Casa del Tejido) also know as "The House of Old Weaving," is both a store and a museum. The museum section features traditional clothing from Guatemala’s indigenous people, while the store sells the colorful, vintage clothing from various regions of the country.