The Twi'lek Resistance, alternatively known as the Twi'lek freedom fighters, comprised a group of rebel Twi'leks who fought against the Separatist Alliance's control of the planet Ryloth during the Clone Wars. Under the leadership of Cham Syndulla and with assistance from the Grand Army of the Republic, the Twi'leks successfully liberated their homeworld from Separatist forces.
The resistance took shape and was spearheaded by political figure and General Cham Syndulla when the Confederacy of Independent Systems invaded Ryloth. Subsequently, the resistance fought alongside the Republic garrison commanded by Jedi General Ima-Gun Di and Captain Keeli in opposition to the Droid Army. Regrettably, the resistance and the garrison experienced dwindling supplies.

Syndulla was of the belief that the Republic had forsaken them, a notion that Di refused to accept. Consequently, the resistance chose to retreat across the mountains together with their families. While Di and the remaining members of the Republic garrison remained to fight, the Resistance, accompanied by their families, escaped over the mountain range. They received provisions and medical aid from Republic blockade runners dispatched by Senator Bail Organa of Alderaan.
In the wake of the initial invasion, a significant number of Twi'leks were killed in a massacre. The resistance then erected grave markers in remembrance. During this time, they obtained intelligence from their spies indicating that Separatist Council member, Emir Wat Tambor, had given orders for his forces to plunder treasures from their settlements.
Following the Republic's return to Ryloth, the Resistance launched an attack on a droid patrol, successfully destroying them near their hideout. Subsequently, they surrounded Jedi General Mace Windu and his ARF troopers. Initially, Syndulla and the resistance were reluctant to collaborate with Windu's forces. However, they reconsidered their stance when Commander Ponds made them aware of Tambor's firebombing campaign that had devastated numerous villages. After a discussion with Senator Orn Free Taa, Syndulla and the Resistance decided to join Windu's forces in the effort to take Lessu.
After expelling the Separatists, the Republic took control of the planet. With the conclusion of the Clone Wars, the Republic was superseded by the Galactic Empire, which established a protectorate over Ryloth. Although the planet maintained nominal independence and continued to be represented in the Galactic Senate by Senator Orn Free Taa, the true authority resided with Moff Delian Mors. While Taa and various collaborators reaped benefits from Imperial rule, many Twi'leks grew to resent the Imperial presence. Cham, along with like-minded Twi'leks, established the Free Ryloth Movement, which initiated a rebellion against the Empire.