Safavid relations with their neighbors during the reign of Shah Safi experienced a period of military conflicts and border disturbances, although the Uzbek invasions of Khorasan did not achieve anything for them, the Ottoman government separated Baghdad from Iran and Kandahar also came under the control of Gurkanians. The occurrence of these events was a sign of the weakness and inefficiency of Shah Safi in the administration of the country, which made the neighbors try to implement their goals in the disputed areas after the death of Shah Abbas I. The secession of Kandahar created another chapter in the relations between Iran and India over this state and strained the relations between the Safavids and Gurkanians once again, although it did not lead to a serious crisis in the relations between the parties. In this study, the relations between the Safavids and the Gurkanians during the era of Shah Safi and Shah Jahan, the causes and contexts, especially the conflict over Kandahar and its implications, are examined and analyzed in a descriptive-analytical way. The findings show that Kandahar, as in the past, was the main factor in the formation of bilateral relations, and Shah Jahan's actions to seize this state made the relations between the two governments fragile. However, it did not lead to the complete severance of relations or India's military action against Iran.