The patron saint of Guardiagrele is Saint Donatus of Arezzo, celebrated on 7 August at the Collegiate Church of Santa Maria Maggiore.
The town's other patron 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 also holds the Church of San Nicola di Bari and the Church of Santa Chiara.