At least 60,000 demonstrators gathered outside parliament on Thursday afternoon, waving opposition flags and chanting "resign".
"We have no other way out but to stand here until the end, until the Judas of Georgian politics resigns," Levan Gachechiladze, opposition leader and former presidential candidate, told the crowd.
Shota Utiashvili, a Georgian interior ministry spokesman, told Al Jazeera the police would not be taking heavy action against protesters.
"We believe it's the right of the people who are upset with the government to protest, we respect that right," he said.
Utiashvili said although Saakashvili understood the dissatisfaction of the people, he would not resign before the next election, which is set for 2013.
Matthew Collin, Al Jazeera's correspondent in Tbilisi, said despite the protests, Saakashvili had retained a core of supporters.
"There are signs that Saakashvili does still have an element of popularity," he said.
"Also, a lot of Georgians simply want stability.
"They're tired of endless protests in the street, they want to get on with their lives and they want the economy to develop, and they feel political unrest won't allow that to happen."
Call for unity
Thursday's mass rally coincides with the 20th anniversary of a bloody crackdown by Soviet troops that left 20 dead.
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| At least 50,000 protesters demonstrated outside parliament in Tbilisi on Thursday [AFP] |
Saakashvili called for unity as he gathered with hundreds of people in front of the parliament to commemorate the 1989 massacre.
"Georgia today, as never before, needs unity and firmness," he said.
"We are a democratic state and people have different opinions."
A Georgian opposition party said about 60 of its activists had been arrested overnight in Rustavi, a town near Tbilisi.
Khatuna Ivanishvili, a party spokeswoman for the Democratic Movement-United Georgia party, said: "Obviously this happened to stop them from coming to the protest."
Georgian police have denied the claim.
Opposition to the president has been growing since last year's Russia-Georgia war, with many accusing Saakashvili of mishandling the conflict.
Critics have also accused the president of betraying the democratic reforms promised in the 2003 "rose revolution", in which he came to power.
Irakli Alasania, a former Georgian envoy to the UN and key opposition leader, said: "There is going to be a huge amount of the population involved in the protest rallies.
"We need to now see if the president is willing to listen to his own people, learn from the mistakes of the past and be adequate and respectful to their demands."