Madtha was travelling back from the northwestern town of Odienne to an ordination ceremony in the country’s west on Saturday evening when his car collided with another vehicle.
“Unfortunately the apostolic nuncio died on the spot,” said Mathieu Tehan, spokesman for the western diocese of Man where the ceremony was to take place.
President Alassane Ouattara, in a statement read on national television, expressed his “deep regret” at the death and sent condolences to the church and Madtha’s family.
Madtha, born in 1995 in the southwest Indian state of Karnataka, became the doyen of the Ivorian diplomatic corps after arriving in 2008.
He tried to play a behind-the-scenes mediating role during Ivory Coast’s 2010-11 political crisis when the previous ruler, Laurent Gbagbo, refused to step down even though Ouattara was declared winner of presidential elections.
The Catholic church was put in a delicate position since some of the country’s bishops favoured Gbagbo, who comes from the country’s majority Christian south.
Ouattara is from the largely Muslim north.
Last month Ouattara, accompanied by his Christian wife, met Pope Benedict XVI in Rome.
Ivory Coast and the Vatican agreed on “the role that the Catholic Church can offer for the good of the country, by encouraging and promoting human rights, dialogue and national reconciliation”, the Vatican said in a statement at the time.
Gbagbo is now awaiting trial for crimes against humanity at the International Criminal Court in The Hague.
Around 40 percent of Ivory Coast’s population is Muslim and 40 percent Christian. Some 20 percent are believers in native religions.