After his release from prison in 1912, Gyulkhandanyan studied law․ Two years later he graduated and married his wife Haykanush, with whom he had a son, Ruben. Along with ARF founder Stepan Zorian, he organized the defense of Baku against the Turkish offensive in 1918. After the establishment of the First Republic of Armenia in May 1918, Gyulkhandanyan became a member of parliament and the ARF-led government, where he occupied the posts of Minister of Internal Affairs, Justice, and Finance. In December 1920, as the First Republic faced a double assault by Turkish and Soviet troops, Gyulkhandyan was one of the delegates who signed the Treaty of Alexandropol with Turkey, which was never ratified but essentially realized a year later through the Treaty of Kars, albeit with less harsh territorial losses for Armenia.