St. Paul had also sent one of his most famous letters to the church in Ephesus. Additionally, St. Jean and Virgin Mary visited Ephesus and Virgin Mary settled down the Mount Bulbul, located close to Ephesus, around the years of 431 AD. Ephesus became a state of Seljukian in the year of 1090, for a time was held by Byzantine. In 1307 Seljukians controlled the city again. But,  years later, the River Caystros was silted up, leaving the site far inland. Therefore, the city of Ephesus has lost its significance, due to the development of the ports of Izmir and Kusadasi in sea trade.

  
Alexander the Great won Persians and the Ionian cities got their independence in the year of 334. Ephesus was in great prosperity during the times of Alexander the Great Until the arrival of Alexander the Great, Ephesus was consisted of two governing systems, democratic and oligarchic. But the oligarchic system was violated with the coming of a new ruler, and a rebellion existed in Ephesus. The Temple of Artemision was fired and destroyed by the supporters of oligarchy in 356BC.

As the temple became unusable, Alexander the Great proposed for repairing. But the Ephesians delicately refused for the reason that "A God can not built a temple for a God." An Ephesian architect, Dinocrates restored the Temple of Artemision. After the death of Alexander the Great, Ephesus was ruled by the general of him, Lysimakhos, in 287 BC.  
 
Lysimakhos decided to change the prior location of Ephesus to further west, due to the destruction of the port by the alluviums, and the inhabitants were forced to settle in the new place named "Arsinoeina", the name of Lysimakhos’ wife. The city was surrounded by wide stone walls in 10 meters height and 9 meters length. With the death of Lysimakhos, Ephesians destroyed most of the city walls. And, "Arsinoeina" was changed into "Ephesus" again, to be forgotten eternally.