The town dates back to prehistoric and italic times. It was under the Lombard rule in the IX century. After the Normans the Angevins came, then the Aragoneses. In 1391 Guardiagrele was granted the right to mint its own coins. The town is famous for handicraft production, especially in metalworking. In fact, the presentosa, a typical Abruzzese jewel, is produced in Guardiagrele. In the XV century the town gave birth to the goldsmith, engraver and painter Nicola Gallucci, called Nicola da Guardiagrele. His masterpieces, crosses and monstrances, enrich the collegiate church of Santa Maria Maggiore. Other places of interest in Guardiagrele are the church of San Francesco, the church of San Nicola di Bari, probably the oldest in the city, the church of San Silvestro, now used for exhibitions, conferences and concerts, the convent of the Capuchins; the church of San Rocco, the church of Santa Maria del Carmine, in Modesto della Porta (famous local dialect poet) street, the church of Santa Chiara, the church of San Donato (the patron saint), the city gates (San Giovanni, San Pietro and the gate of the Wind or of Grele) towers (Orsini, Adriana, Stella, Santi Pietro and Gastaldo). In the locality Comino there is an Italic necropolis.
The museums of Guardiagrele are: the Civic Museum, the Museum of the Duomo, the Museum of the Customs and Traditions of Our People and the Archaeological Museum. Sise delle monache (nuns’ tits) is a typical cake from Guardiagrele.