Destexhe was a member of the liberal Mouvement Réformateur (MR) and represented Belgium in the World Economic Forum.

He was then confronted with many international crises: Bosnia, Iraq (1st Gulf War), Rwanda (genocide, 1994), Somalia (famine).

In addition to his role in the Senate, Destexhe has been serving as member of the Belgian delegation to the Parliamentary Assembly of the Council of Europe since 2014.

Since 2016, he has been serving as chairman of the Assembly's Committee on Legal Affairs and Human Rights as well as of its Sub-Committee on Conflicts between Council of Europe Member States.

Desthexhe is also currently a board member of The Parliamentary Network on the World Bank & International Monetary Fund.

In March 2017, Desthexhe caused controversy when he joined Pedro Agramunt and Jordi Xuclà on a visit to Damascus amid the Syrian civil war.

[11] Destexhe has published a number of books, including one, translated into English, dealing with the Rwandan genocide.

Destexhe stated that Dallaire failed to protect his troops and cost the lives of ten Belgian Blue Helmet soldiers in UN service.