He also repeated claims that "external" influence was behind at least some of the popular upheaval.
During a Friday sermon read by an aide in Karbala, Sistani described the ongoing anti-corruption protests in Baghdad and several other central and southern cities as a "reformist movement." He reiterated his call for authorities to hold to account members of security forces responsible for killing demonstrators.
"The political forces in power have a unique opportunity to respond to the demands of the citizens according to an agreed roadmap which will be implemented in a certain period of time, putting an end to a long era of corruption, abhorrent quotas, and the absence of social justice," Sistani said.
"It is not permissible to delay and procrastinate in this area, because of the great risks afoot in the country."
"Maintaining the peaceful nature of the protests in all its forms is of great importance," the cleric added.
"It is the responsibility of the security forces to avoid using violence, especially excessive violence, in dealing with peaceful protesters."
Since they began early last month, the widespread protests have resulted in the deaths of at least 270, while some 12,000 have been injured.
Many have been killed after being struck in the head by military-grade gas canisters. Others have been killed in crowds by live fire.
Iranian-backed Popular Mobilization Force (PMF) militias have also reportedly deployed fighters to deter protests, killing multiple demonstrators with sniper rounds.
Social media activists have circulated gruesome videos purporting to show many such incidents.
Protesters are calling for a radical change in Iraq's governance, which they say has repeatedly failed to address their needs and instead serves the interests of a small governing elite.
They also lament foreign influence in Iraq's internal affairs, with the main target of discontent being Iran, which has entrenched itself in Iraqi politics, including through various proxies such as PMF militias.
In early November, Sistani implicitly stated his opposition to Iran's interventionist exercises in Iraq, stating, "it is not for any person, group, party or any regional or international party to seize the will of Iraqis in this and impose their opinion on them."
This came amid a Reuters report saying notorious Iranian military commander Qassim Soleimani had been in Baghdad to prevent efforts to remove Iraqi Prime Minister Adil Abdul Mahdi from power.
On Friday, Sistani repeated the warning, saying internal and external parties are seeking to take advantage of the movement, and urged demonstrators to "be very cautious of exploiting these entities and parties to any loophole through which they can penetrate their gathering and change the course of the reform movement."
Editing by John J.