Among the patrons of Guardiagrele is Saint Nicholas the Greek, celebrated on the third Sunday of May; his relics, of the saint who died between 1009 and 1012, are kept in the Church of San Francesco.
The town's other patron, Saint Donatus of Arezzo, is instead celebrated on 7 August at the Collegiate Church of Santa Maria Maggiore. The town also holds the Torrione Orsini and the Torre Adriana.