Dealing with enemies is one of the central themes in the teachings of the Holy Quran, which developed and gradually took shape within the historical context of the mission of the Great Prophet (PBUH). During this period, groups such as the disbelievers, polytheists, Jews, and hypocrites emerged as the primary threats to the Islamic call. This article aims to examine the approaches employed by the Holy Quran in confronting these groups during the prophetic era. The main research question is: what methods and strategies did the Holy Quran utilize to deal with enemies during this period? The research is qualitative in nature, and data were collected and analyzed using a documentary method and thematic analysis. The findings indicate that the Holy Quran adopted a phased and combined approach in dealing with the enemies of Islam; such that it first emphasizes soft methods such as tolerance, clarification, education, and propagation, and if these methods prove ineffective, it resorts to hard struggle and jihad. Furthermore, the Quran, considering the nature of each enemy group, prescribed a specific method for confronting them and recommended an appropriate strategy for each type of threat.