In 2011, Del Castillo starred as Teresa "La Mexicana" Mendoza in the Telemundo telenovela "La reina del sur" based on a novel of the same name by Spanish author Arturo Pérez-Reverte, a role that skyrocketed her fame across Latin America. With a $10 million budget it is the second most expensive telenovela ever produced by Telemundo. The series later was renewed for a second season, that premiered in 2019. del Castillo continued her collaboration with Telemundo in 2015, starring in "Duenos del Paraiso." The telenovela is inspired by the drug trade of Miami in the 1970s. She also appeared in a number of American television shows, include "", "Grimm" and "Dallas". In 2015, she had a recurring role as Rogelio de la Vega's ex-wife in the CW comedy series, "Jane the Virgin".