Surah Al-Mumtahanah, a Madani surah of the Quran, was revealed at a time when the Islamic government was being established and official relations with followers of other Abrahamic religions and Mushriks were in the offing. It emphasized the need for Muslims to learn the principles of socio-political life. One of the goals of this Madani surah was to reform relationships and replace them with rationality in social interactions. Al-Mumtahanah, a short surah with 13 verses, was revealed with the aim of enlightening people about the dividing line between kufr and faith. This surah discusses the rulings on the type of relationship with disbelievers, the necessity of severing friendship with those who are hostile, and the determination of the fate of those who migrate to Muslim lands. Ayatollah Khamenei, a jurist and interpreter with a comprehensive approach and an emphasis on religious governance, has interpreted the surah in light of international relations and the need to observe the dividing line between kufr and faith among the hostile, and its role in strengthening nations and repelling the dominance of global colonialism. In doing so, he has employed the tool of contemplation and, by applying the verses to the social conditions of future eras, has proven the universality and generality of the Quran. In this way, he has presented a model for reforming international relations and saving humanity from the yoke of colonialism using the principles of human dignity and honor. His views on religious governance have attracted the attention of researchers, which has paved the way for the writing of numerous articles on this subject. The present research, using a descriptive-analytical and library method, compares the interpretation methodology of Ayatollah Khamenei with that of four contemporary Shia and Sunni interpreters, and aims to discover the overall interpretive approach as well as the innovations and political views of His Eminence.