This comes hours ahead of an announcement by US President Donald Trump in which officials said he would recognise the disputed city as Israel's capital.
"I cannot silence my deep concern over the situation that has emerged in recent days. At the same time, I appeal strongly for all to respect the city's status quo, in accordance with the relevant UN resolutions," the pope said, in his weekly address.
The pontiff has called for "wisdom and prudence" in order to avoid conflict, reported the Fox News.
The pope said he was "profoundly concerned" about recent developments regarding Jerusalem, which he called a "special vocation for peace" and a sacred place for Christians, Jews and Muslims.
The pope, who spoke to the Palestinian President Mahmoud Abbas about the crises on Tuesday, made his comments to a group of visiting Palestinians involved in the interfaith dialogue with the Vatican.
At the meeting, the pope said dialogue between all parties would come only through "recognising the rights of all people," noting that the Holy Land was the "land par excellence of dialogue between God and mankind."
"The primary condition of that dialogue is reciprocal respect and a commitment to strengthening that respect, for the sake of recognising the rights of all people, wherever they happen to be," he said.
The US' plan to recognise Jerusalem as Israel's capital has drawn criticism from a number of world leaders who fear it would further escalate regional tensions.
It quickly annexed it, declaring the whole of the city as its capital in a move which has not been recognised internationally.
The Palestinians seek it as a future capital. (ANI)