She is the chairperson of Aware Girls, a global ambassador for Humanists International, and a leading member of the Pashtun Tahafuz Movement (PTM).

In 2019, during the government of Prime Minister Imran Khan, Ismail fled Pakistan and took refuge in the United States after fearing for her life for speaking out against sexual assaults and disappearances allegedly carried out by the Pakistani military.

Malala Yousafzai, the youngest Nobel Prize laureate, who was shot by the Pakistani Taliban at the age of 15 in 2012 because of her activism for female education, was an attendee of Aware Girls in 2011.

We did training that women have human rights and taught leadership skills and how to negotiate with their families and with their parents to get an education and to have control over their own lives.Ismail's organisation widened its scope to include education on topics such as access to HIV and AIDS prevention and treatment, access to safe abortions, and she continues to speak at international conferences to promote awareness of peace-building, tolerance and women's rights.

Both Gulalai and her sister Saba Ismail have also acted as advisers on peace and women's rights to the United Nations and US governmental departments.

The service operates from Peshawar and gives advice on legal and medical aid as well as emergency ambulance information and emotional counseling.

[15][16] Ismail criticised the British government's prevent strategy, saying it could lead to alienation of Muslims and could turn vulnerable individuals towards extremism.

[13] Seeds of Peace was a response to what Ismail saw as the increased "Talibanisation" of young men and women vulnerable to militants in Swabi District and other Pashtun rural areas.

"[8] Between 2009 and 2011, Ismail was on the Executive Committee of the Young Humanists International, and between 2010 and 2012 she was a Board Member of the Women's Global Network for Reproductive Rights.

Aware Girls have been forced to organise their community meetings by invitation only, in hotel rooms protected by armed guards, where they know the owners and staff.

[11]In November 2017, the head of a Pakistani youth parliament in Mardan, Hamza Khan, falsely accused Ismail of blasphemy, a charge which in Pakistan carried the death penalty, and urged his followers to kill her.

[25] Her legal representative petitioned the Islamabad High Court to have her passport and travel documents returned to her and her name removed from the ECL on the grounds that it was a violation of basic human rights.

On 27 January, Ismail visited Khaisor along with five other female PTM activists, Ismat Shahjahan, Bushra Gohar, Jamila Gilani, Sanna Ejaz and Nargis Afsheen Khattak, to express solidarity with Hayat's mother and to also interview the local women about other incidents of sexual harassment.

[37][38][39] On 23 May 2019, as Ismail and other activists were protesting in Islamabad against the murder of Farishta Momand – a 10-year-old Pashtun girl who had been abducted in Islamabad, allegedly raped, and then killed with a knife and thrown in a forest where animals ravaged her body – Ismail became the subject of another first information report for allegedly defaming state institutions during the protest rally against Farishta's murder.

"[42] Because of the protests against Farishta's murder, Ismail received a 30-day travel ban and a further application was raised to block her social media accounts.

Besides Ismail, the court also issued notices to her fellow PTM leaders Manzoor Pashteen, Ali Wazir and Mohsin Dawar.

Her father told the Voice of America: "Last night, police raided our relatives and family friends’ houses in Peshawar in an attempt to arrest her, but she was not there.

[48] Separately, her father, retired professor Muhammad Ismail, was also charged with sharing "anti-state content" on social media and expressing dissent against the government.

After the hearing of the case, Muhammad Ismail told Al Jazeera: "Honouring the orders of the court, I hereby surrender my right to share my dissident voices on social media, therefore I say goodbye to Facebook and Twitter."

On 2 February 2021, Muhammad Ismail was again arrested on terrorism charges, which rights groups said was part of a sustained campaign of judicial harassment against him.

[5] In recognition of her efforts to further women's empowerment, she received the 2015 Asia Region Commonwealth Youth Award for Excellence in Development, under the theme of Democracy and Human Rights.

[53][54] In 2016, her organisation Aware Girls was awarded the Fondation Chirac Peace Prize for Conflict Prevention, which was presented to Ismail by the then French president Francois Hollande.