At least 60 people have died since the protests began on April 28, according to the ombudsman's office.
The Commission's 48-page report, prepared following a June 6-10 visit by its representatives, detailed allegations of human rights violations.
"The Commission finds that repeatedly, in different regions of the country, the State's response was characterized by an excessive and disproportionate use of force. In many cases the action included lethal force," said the Commission president Antonia Urrejola during a virtual press conference from Washington.
Having spoken to 500 witnesses, the Commission issued several recommendations, including that the government respect the right to protest, an "immediate end to the use of disproportionate force," separating the police from the defense ministry, and an end to a ban on "road blocks as a general form of protest."
The Commission also called for the protection of journalists, who are often the target of attacks, and to compensate victims.
The protests had been 89 percent peaceful, the Commission said.
Colombia President Ivan Duque insisted he was "respectful of peaceful protest" but not "vandalism, low intensity urban terrorism or road blocks."
"No-one can recommend to a country that it tolerates criminality," he added.
Duque has announced a police reform plan, but protesters are angry that it will be conducted by the defense ministry.
The Commission report also included the government's complaint about "infiltrations of the protests by armed third parties."
Authorities claim leftist rebels and drug traffickers have infiltrated the protests to wreak chaos.
But the Commission "noted with great concern a climate of polarization ... that is manifested in stigmatizing speeches" that sometimes come from "public authorities."
Three weeks ago, the most visible organized protest group suspended its demonstrations for a month.
Protesters are demanding a fairer society in a country where the poverty level has risen to 42 percent of the 50 million population.
