The 12 defendants, including Victor Gonzalez, the former pastor of Imperial Valley Ministries -- a non-denominational church that has about 30 affiliate groups throughout the US and Mexico -- were arrested on Tuesday in California and Texas.
They face charges of conspiracy, forced labor, document servitude and benefits fraud.
"The indictment alleges an appalling abuse of power by church officials who preyed on vulnerable homeless people with promises of a warm bed and meals," US Attorney Robert Brewer said in a statement. "These victims were held captive, stripped of their humble financial means, their identification, their freedom and their dignity."
Authorities said the church -- whose stated purpose is to "restore" drug addicts -- lured victims beginning in 2013 with promises of free food, shelter and monetary assistance to eventually return home.
The indictment says that church leaders locked victims inside group homes with deadbolt locks, confiscated their ID papers to prevent them from leaving and stole their welfare benefits.
The victims were required to adhere to a strict set of rules that prohibited them from reading anything other than the bible or discussing "things of the world."
Authorities said church leaders forced the victims to beg up to nine hours a day, six days a week, in some instances by telling them their children would be taken away if they left.
Two of the victims managed to escape, the indictment states. One was a 17-year-old who broke a window and ran to a neighboring property to call police, and the second a woman suffering from diabetes who was allegedly refused medical care.
"This is the most significant labor trafficking prosecution in this district in many years," Brewer said. "These cases are few and far between because many victims live in captivity and fear, powerless to report the crimes against them."
Officials said all of the identified victims have been freed and are receiving assistance.