The following year, de Castro starred in her first titular role, Grazilda (2010), and played Binayaan in the historical epic series Amaya (2011).

[10][11] She has a younger brother, Alchris Galura,[12] who was recognized as Best Supporting Actor by the World Class Excellence Japan Awards (WCEJA) for his role in the drama series Abot-Kamay na Pangarap.

[17] On January 27, 2001, de Castro made her entry into GMA Network, debuting on the television variety show Master Showman Presents and subsequently becoming one of its regulars.

[17] De Castro began her career with GMA Network, playing a minor role in the soap opera Ikaw Lang ang Mamahalin.

Between 2002 and 2005, she appeared in films sporadically, playing bit parts in the movies Singsing ni Lola (2002),[18] Bahid (2002),[citation needed] and Miss Pinoy (2005).

[24] De Castro played Clara, an expert on history and geography who would use this knowledge to help the main characters find the titular treasures.

Film critic Tito Valiente of Business Mirror noted her portrayal of Emma as "one reason the short life on that island becomes very real."

[26] That same year, she also played a supporting role in the romantic film Batanes: Sa Dulo ng Walang Hanggan alongside Iza Calzado, Taiwanese singer-actor Ken Chu, and Marky Cielo.

[31][32] After another supporting role in the television adaptation of comic-book writer Carlo J. Caparas' graphic novel Gagambino, de Castro once again landed a lead role in another television adaptation of a Filipino film, Kung Aagawin Mo ang Lahat sa Akin, opposite Patrick Garcia, Maxene Magalona, Jackie Rice, and JC Tiuseco.

[34] Shortly after, she landed another role in the Philippine remake of the Korean television series Stairway to Heaven alongside Dingdong Dantes, Rhian Ramos, and TJ Trinidad.

The first was the independent political thriller Bente, where she replaced former StarStruck contestant and fellow GMA actress Jewel Mische when the latter refused to film a sex scene she considered "beyond [her] moral standards"[37] as directed by Mel Chionglo.

The film, directed by Jun Lana and top-billed by Marian Rivera and Dennis Trillo, is about a girl who can predict the future using tarot cards.

The production was received warmly, with Noelani Torre of the Philippine Daily Inquirer noting its "fascinating subject matter," "colorful cast," and "visual richness and clarity.

"[44] The fourth film de Castro starred in 2009 was the independently-produced Astig (international title: Squalor) alongside Sid Lucero, Edgar Allan Guzman, Arnold Reyes, and Dennis Trillo (who also served as director).

In Astig, de Castro played Elgine, a teenager afflicted with a sexually transmitted disease who eventually becomes the love interest of Trillo's character.

[47] Darwin Chiong of GMA News called the film's cinematography "remarkable" and praised the cast as a whole, saying, "The movie gathers an ensemble of actors that deliver in the acting department, even those in supporting roles like Glaiza de Castro and Malou Crisologo.

The show, which also starred Regine Velasquez, Mark Anthony Fernandez, TJ Trinidad, and singer Jaya, and is partly based on the American movie trilogy High School Musical and the American television series Glee, saw de Castro playing the ambitious Tiffany, who is Lady's (Rufa Mae Quinto) assistant and soon-to-be a villainess to singer-actress Regine Velasquez's heroine Melody.

In light of the show's success, de Castro's manager, Manny Valera, has decided to turn down any further villain roles on behalf of his talent to build her up as a lead star.

[citation needed] De Castro later played Binayaan in the epic drama Amaya, opposite Marian Rivera and Sid Lucero.

In 2012, de Castro first appeared on Tweets for My Sweet, playing the role of Kimberly, Meg's (Marian Rivera) long-lost daughter and sister.

[citation needed] In the third quarter of the year, she was chosen to play the role of Heidi, which was originally intended for Alessandra de Rossi, in the Philippine adaptation of Temptation of Wife.

[55] In 2015, de Castro played Althea Guevarra in the lesbian series The Rich Man's Daughter alongside Rhian Ramos.

In 2017, de Castro released her fourth album, Magandang Simulain, under PolyEast Records and held a concert at the Music Museum in San Juan, Metro Manila, to promote it.

[citation needed] De Castro received critical acclaim for her in-character covers of the Asin songs "Himig ng Pag-Ibig" and "Pagbabalik" when she played anti-dictatorship activist Cecilia Flores-Oebanda in the 2018 film Liway.

"[49] Although De Castro considered posing for magazines such as FHM "for instant fame and fortune," she eventually decided against it, instead opting to develop her skills as a serious actress, saying, "I just want to start on the right foot by focusing more on acting than diverting my attention to other interests.

[67] After performing the role of anti-Marcos activist Cecilia Flores-Oebanda in 2018, de Castro has spoken against historical negationism regarding the Philippines' martial law era, which was the film's setting.

"[68] In 2020, de Castro participated in activities denouncing the then-newly signed Anti-Terrorism Act of 2020, joining numerous artists in reciting Charlie Chaplin's final speech in the film The Great Dictator, translated into Filipino by writer Rody Vera.