Resistance is a central theme in In the Time of the Butterflies, highlighting the courage of the Mirabal sisters against the oppressive regime of Rafael Trujillo in the Dominican Republic. The novel dramatizes their struggle, showing how they became symbols of defiance and the price they paid for their bravery. Through their story, the book illustrates the necessity of standing up against tyranny, even at great personal cost.

The Mirabal sisters, Minerva, Mate, and Patria, are drawn into the resistance movement as they witness the injustices of Trujillo's dictatorship. Their involvement begins through connections with revolutionary figures like Lio and grows as they become more aware of the regime's brutality. Minerva and Mate actively participate in the underground movement, risking their lives and enduring imprisonment. Their actions demonstrate a steadfast commitment to fighting for freedom and justice.

Patria's journey to resistance is marked by a profound personal transformation. Initially loyal to Trujillo, her faith is shaken after witnessing a massacre of young rebels. This event becomes a turning point, leading her to join her sisters in the fight against the regime. Her conversion is symbolized in a powerful moment when she realizes the need for rebellion:

"The time was now, for the Lord had said, I come with the sword as well as the plow to set at liberty them that are bruised."

The sisters' resistance ultimately leads to their assassination, a testament to the threat they posed to Trujillo's power. Despite their tragic end, their legacy endures through Dedé, the surviving sister, who carries their story forward. The novel portrays the Mirabal sisters as "the butterflies," a symbol of transformation and hope, emphasizing the enduring impact of their resistance. Their story serves as a reminder of the sacrifices made in the pursuit of freedom and the enduring spirit of those who dare to defy oppression.