Pope Francis has warned that the world sees Europe as "somewhat elderly and haggard" during a speech to the European Parliament in Strasbourg.
The Pope said the continent felt "less and less a protagonist", in a world that regarded it with mistrust.
He also called for a "united response" to the help the boatloads of migrants arriving in Europe.
Pope Francis's whistle-stop visit to Strasbourg disgruntled some, who accused him of neglecting Europe.
Many of Strasbourg's Catholics were upset that the Pope would not meet them or visit the city's cathedral.
The four-hour visit - the shortest made by any Pope abroad - was his second European trip since his election last year. He travelled to Albania in September.
Addressing the Parliament on Tuesday, the Pope called for action following the deaths of thousands of migrants who have drowned while trying to cross the Mediterranean.
"We cannot allow the Mediterranean to become a vast cemetery," he said.
"The absence of mutual support within the European Union runs the risk of encouraging... solutions which fail to take into account the human dignity of immigrants, and thus contribute to slave labour and continuing social tensions."
The treatment of migrants was a subject he also touched on during a second speech at the Council of Europe, Europe's main human rights body.
His remarks came as the Greek authorities said they were trying to rescue a cargo ship, believed to be carrying some 500 migrants, that was adrift off the eastern Mediterranean island of Crete.
The Pope also used his visit to Strasbourg to call for the creation of jobs and better conditions for workers.
At the European Parliament, he spoke of a need to reinvigorate Europe, describing the continent as a "grandmother, no longer fertile and vibrant" and saying it risked "slowly losing its own soul".
"The great ideas which once inspired Europe seem to have lost their attraction, only to be replaced by the bureaucratic technicalities of its institutions," he said.
Pope Francis left his Popemobile behind on Tuesday, instead opting for a French-made Peugeot 407 family car.
Residents in Strasbourg were told they could watch both the pontiff's speeches on a giant screen installed inside the cathedral, which is celebrating its millennial anniversary.
One worshipper told Reuters: "I think there is disappointment but I think he also has reasons for making his decision.
"He knows what he is doing but we would have liked him to be here."
It was the second time a Pope has visited Strasbourg.
In 1988 Pope John Paul II visited the city and addressed the European Parliament, where he was heckled by Northern Irish MEP the Rev Ian Paisley.
During his speech the late Pope called Europe "a beacon of civilisation".