The demonstrators, estimated to number around 6,000, marched towards the House of Representatives compound, where Duterte gave his last state of the nation address before Congress.
They held banners with anti-Duterte messages such as, "Enough is enough! End Duterte regime now!" and paraded effigies of Duterte as a monstrous octopus, a gecko, and a beheaded king.
Duterte's six-year presidency ends next year, but he has said before he is open to running for vice president because it would give him immunity from any criminal suits that might be brought against him when he steps down.
Activists denounced the "bloody legacy" of Duterte's term, a reference to the killings under his controversial crackdown on illegal drugs and other alleged human rights violations.
"We say 'no more!' to a Duterte kind of governance," said Cristina Palabay, secretary general of human rights group Karapatan, which was among dozens of organisations that joined demonstrations in Manila.
"We will not let him get away with mass murder and state repression, and we vow to not let his successor claim victory in the coming elections," she added. "We must end Duterte’s reign of terror ... and hold him to account for his crimes against the Filipino people."
Presidential spokesman Harry Roque said 76-year-old Duterte was not expected to discuss his political plans in 2022 during his speech, and instead would detail the roadmap for the country's recovery from the Covid-19 pandemic.
"If he does, it would probably be as part of his assessment if there [is] unfinished business or not," he told a Manila radio interview ahead of the speech.
"The speech will focus on the achievements and proposed laws, including the creation of a virology institute and a centre for disease control to institutionalize our response in case of another pandemic," he added.
More than 27,000 people have died and over 1.5 million have fallen ill with Covid-19 in the Philippines, and experts have warned of a new surge in cases due to the more contagious Delta variant.
Roque said the address would be Duterte's "valedictory" speech, where he would also summarize his administration's progress in the key campaigns against illegal drugs and corruption.
"The president would probably admit that the illegal drugs problem was worse than he expected," he said. "Yet, 60 per cent of our communities are now drug-free ... There [has been] a lot of progress in the war against illegal drugs."
More than 7,000 people have been killed in police operations against illegal drugs in the Philippines in the past five years. Human rights groups have alleged that the toll could even be three times that number.
Questions have also arisen about whether the suspects were extrajudicially killed by police and whether some of those killed actually had any role in drug sales. - dpa