In 1509, the major Battle of Diu (1509) took place between the Portuguese and a joint fleet of the Sultan of Gujarat, the Mamluk Sultanate of Egypt, the Zamorin of Calicut with support of the Ottoman Empire. Since 1517, the Ottomans had attempted to combine forces with Gujarat in order to fight the Portuguese away from the Red Sea and in the area of India. Pro-Ottoman forces under Captain Hoca Sefer had been installed by Selman Reis in Diu.

Diu in Gujarat (now a state in western India), was with Surat, one of the main points of supply of spices to Ottoman Egypt at that time. However, Portuguese intervention thwarted that trade by controlling the traffic in the Red Sea. In 1530, the Venetians could not obtain any supply of spices through Egypt.

The siege of Diu occurred when an army of the Sultanate of Gujarat under Khadjar Safar, aided by forces of the Ottoman Empire, attempted to capture the city of Diu in 1538, then held by the Portuguese. The Portuguese successfully resisted the four months long siege.

The defeat of the combined Turkish and Gujarati forces at Diu represented a critical setback in Ottoman plans for expanding their influence into the Indian Ocean. Without a suitable base or allies, failure at Diu meant the Ottomans were unable to proceed with their campaign in India, leaving the Portuguese uncontested in the western Indian coast. Never again would the Ottoman Turks ever send so large an armada to India.