Handžić was the leader of the Islamic revivalist movement in Bosnia and the founder of the religious association El-Hidaje.

He withdrew his support several months later and initiated the adoption of the Resolution of Sarajevo Muslims condemning the war crimes committed by the Independent State of Croatia.

Handžić later became the chairman of the Council of National Salvation, which was created to organize defense and aid for Muslims of Bosnia.

The Society of Gajret awarded him a scholarship towards medical studies for finishing Sharia Grammar School as the best student of his year.

A year later, he wrote a booklet entitled Vasijjetnama (English: Will) and donated all of the income from that work to Merhamet.

[12] Handžić's political career began when he was a candidate on the Muslim Organization (Bosnian Muslim branch of the Croatian Peasant Party) electoral list which was part of an opposition coalition led by the Croatian Peasant Party in 1938 parliamentary election.

Handžić later participated in several meetings of major Bosnian cultural and religious organizations which led to the creation of the Movement for the Autonomy of Bosnia and Herzegovina[b] on 30 December 1939.

[15] This included Handžić, who together with Kasim Dobrača, pledged allegiance to Poglavnik Ante Pavelić in May 1941 on the behalf of El-Hidaje.

[16] However, this support was withdrawn on 28 August, when during an El-Hidaje assembly Handžić initiated the adoption of a resolution condemning Ustaše war crimes and the expulsion of Serbs, Jews, Romani and other people from Bosnia and Herzegovina.

[18][19] Handžić accused the Nazi-puppet Ustaša regime of murdering Muslims, and asked Germany to intervene.

[21] During the same month, Handžić welcomed the Grand Mufti of Jerusalem, Amin al-Husseini at a banquet in the Sarajevo city hall.

[14] Handžić strongly opposed the westernization of Bosnia, calling it "materialistic", and condemned pre-marital sex and consumption of alcohol.

[28] Mehmed Handžić died during a routine medical operation in Koševo Hospital on 29 July 1944, at the young age of 37.

[1] It has been alleged that the death was a result of an assassination by the Partisans; historian Marko Attila Hoare describes the theory as "not impossible".

[1] Handžić's bibliography amounted to 300 books and numerous articles, treatises, essays, brochures and textbooks both on Bosnian and Arabic.