A ceasefire between the Syrian government and armed opposition groups was reached in late December. It was brokered by Russia and Turkey, now seen as guarantors of the agreement, and despite some violations, it has held longer than any others since the war began almost six years ago.
ISIS and Jabhat Fateh al-Sham, formally known as Jabhat Al Nursa, are listed by the UN as terrorist groups and were not included in the ceasefire.
"The ceasefire is holding more than previous ones. And, in my modest opinion, has -- if we all look at it carefully and support it -- more chances to actually succeed than others," de Mistura told delegates Sunday at the Munich Security Conference in Germany.
"It's time to try again some intra-Syrian talks," he said, adding the United Nations must see if there is any "space for a political discussion." UN talks on Syria are scheduled to begin in Geneva on Thursday.
"What I do know, (is) that we have to push for the momentum. Because even a ceasefire with two strong guarantors cannot hold too long if there's not a political horizon," he said.
"If you want to defeat Daesh, we need -- even if it looks complicated, even if it looks remote -- a political, inclusive, credible solution in Syria," he said, referring to ISIS by its acronym in Arabic. ".And that's the challenge we are going to face in the next few weeks."
In his address, de Mistura said that the United States' future involvement in the Syrian conflict and political talks remained a "big question mark."
"Where is the US in all this?" he asked.
De Mistura said that he understood that talks were going on in Washington on how to balance fighting ISIS while limiting the influence of some regional players and not damaging allies at the same time.
He did not specify which countries he was referring to, though Iran, Turkey and Russia are all playing major roles in the conflict.
The United States' anti-ISIS special envoy, Brett McGurk, spoke after de Mistura and said that his country was looking to help reinforce the Syrian ceasefire rather than taking an active mediation role.
McGurk also spoke about why a ceasefire agreement last year failed.
"One of the reasons why this process did not succeed as we had hoped is frankly because we were a guarantor and Russia was a guarantor. It turns out, when the US is a guarantor -- we don't have people on the ground -- we became a bit of a ping pong ball to try to control the situation," he said.
"Turkey and Russia are suitable guarantors and we are looking for a role that the US can come in to help reinforce that process through Astana."
Recent peace talks in Astana, Kazakhstan, have focused on maintaining the current ceasefire deal.
It is not yet clear how involved the United States will be in the Syria conflict or political talks under President Donald Trump. But Trump has repeatedly said he disagrees with trying to fight ISIS and push out Syrian President Bashar al-Assad at the same time.
Trump has called for safe zones within Syria for refugees fleeing violence as a way to stem and even reverse the migration of Syrians to Europe and elsewhere.