With a presence since the 2nd Byzantine period, Karkadiotissa is a village that stands the test of time, unlike most small villages in Crete that slowly fade away. Its mountainous character seems to give it life as its inhabitants are systematically engaged with livestock and agriculture, especially olive and grape crops.

The oldest reference to the village is found in a document of 1268 where the name of Papa Nicola de Carcariotissa is mentioned. It is also found in the Inventory of Churches and Monasteries of 1320, as well as in all subsequent census lists. During the period of the Venetian occupation, the village was divided into Upper and Lower Karkadiotissa, a division that no longer exists.

Despite its close proximity of the Monastery of Epanosifi and the deserted monastery of Astratigos, its residents identify with Panagia Kardiotissa, from whom their village took its name. Only a few ruins of the old church of Panagia remain, nearby the modern church that celebrates on September 8 with a big festival and a traditional feast in the village. Its inhabitants seem to enjoy both dancing and singing. It is no coincidence that Karkadiotissa is the birthplace of the well-known poet Michalis Stavrakakis or Michalos, whose verses have been set to music and sung by the greatest Greek composers and singers.