The 49-year-old, sporting a salt-and-pepper beard, recited a verse from the Koran and thanked those assisting him, saying "God bless you", video footage showed.
The commission released pictures showing Seif al-Islam dressed in a traditional Bedouin robe and headdress. He was issued with a voter registration card for the southern Sebha district.
First reactions on the streets of the capital Tripoli were negative.
"Instead of resolving the problem this only complicates things further," said Nizar al-Hadi, 33. "It's just not right!"
Ramzi Douess said he did not doubt that some people would accept Seif's candidacy, but questioned what route he would lead the North African country on if he won.
"Will he accept Libya as it is today, or will he take it backwards?" Douess asked.
Libya opened registration for candidates in presidential and parliamentary polls last Monday.
Both are slated for 24 December, but in early October parliament split the dates of the vote by postponing legislative elections until January.
Foreign powers have been pushing hard for both elections to be still held on the same date, as agreed at UN-led talks last year.
Speculation had been mounting for months over a possible presidential bid by Seif al-Islam, who was also sentenced to death by a Tripoli court in 2017 for crimes committed during the revolt.
In July, Seif al-Islam emerged from years in the shadows and told The New York Times he was planning a political comeback.
In a rare interview, he said he wanted to "restore the lost unity" of Libya after a decade of chaos.
"I've been away from the Libyan people for 10 years. You need to come back slowly, slowly. Like a striptease. You need to play with their minds a little," the paper quoted him as saying.
Until the interview, Seif al-Islam had not been seen or heard from since June 2014, when he appeared via video link from Zintan, in the west of the country, during his trial by the Tripoli court.
Although the court sentenced him to death in absentia, a rival administration in the east pardoned him.
The militia that was holding him in Zintan has repeatedly refused to hand him over to The Hauge-based ICC, and freed him in 2017.
A spokesman for the ICC, Fadi Abdallah, told Libya's Al-Ahrar television that the court still wants Seif al-Islam.
Analysts say Seif al-Islam's bid for the presidency will be problematic for Libya's electoral process.
"This is only going to complicate the electoral process further," said Wolfram Lacher, a senior associate at the German Institute for International and Security Affairs.
World powers meeting in Paris warned Friday that Libya was at a "crossroads" which would determine its future.
"We urge all Libyan stakeholders and candidates to respect their commitments towards holding elections on 24 December 2021 (and) to accept the results of free, fair and inclusive elections," they said.
Despite a year of relative peace following a ceasefire between eastern and western camps, the process has been overshadowed by wrangling over the legal basis for the polls and the powers attached.
Some also expect possible presidential bids by eastern-based military chief Khalifa Haftar and current prime minister Abdulhamid Dbeibah.
Former interior minister Fathi Bashagha has confirmed he will run, while others expected to do so include two diplomats and a comedian.