University lecturers and students blocked parts of the road around the Msida skatepark in protest on Friday.
Holding placards reading "assassins", "blood is on your hands" and "Muscat kriminal" (Muscat is a criminal), they later moved their sit-in protest to Regional Road.
One banner read "Daphne should be here". Chants of "assassini" and "ġustizzja" could be heard over the sound of car horns of disrupted traffic.
This is the latest in a series of protests that have been held in Malta in the wake of a political crisis sparked by the Daphne Caruana Galizia murder investigation.
The students said the protest, which lasted around 45 minutes, was aimed at calling for justice for Ms Caruana Galizia and decried the lack of action taken against people like the former chief of staff Keith Schembri.
Civil society groups, including Repubblika and Occupy Justice, joined the protest.
The organisers of the protest remain unknown.
Speaking to Times of Malta, students said that they were joining the protest because they were fed up of the corruption in the country, the bi-partisan nature of its politics and the need to raise their voices and show the Prime Minister that they were not happy with their democracy.
One male student said he felt that students were not properly represented by the current protests and that it was time for them to cast aside partisan politics.
"It is not the time for tribalism. It is the time to stand up for what you believe in, for our rights. Corruption has been happening for years. It is too much," he said.
Belle, a Dutch international relations student, told the Times of Malta that she was impressed by the turnout and what it showed.
“This protest was organised very last minute, very low key. There was no event organised, it was just people passing the message along, spreading the message. The fact that there are at least 100 people who are in the loop, who are willing to show up, who are taking their time to come to here for Malta. It’s very radical and I think it shows that people are starting to care more and more," she said.
“I see the relevance of these protests because bi-partisanship has prevented people from going out on the streets and the fact that this is happening right now and in a European context, is huge,” she added.