Ronaldo played 65 minutes of his country's final World Cup friendly after missing a couple of games amid fears he might not be fully fit for the start of the tournament in Brazil.
Raul Meireles also returned to the side after injury, giving coach Paulo Bento a full squad to choose from for the first time in the build-up to their tough Group G campaign against Germany, Ghana and the United States.
Ronaldo was quickly off the mark against a Republic side lacking a lot of expected starters, forcing a save from keeper David Forde inside the first minute.
Portugal took the lead with their next attack as Silvestre Varela crossed from the right for Hugo Almeida to head past Forde.
Ronaldo drew gasps from the crowd when he slipped awkwardly, but he soon picked himself up off the turf and hit the post with a shot on 19 minutes.
Seconds later Portugal were 2-0 up with Forde helpless to keep out a Fabio Coentrao cross deflected off defender Richard Keogh.
Ronaldo provided an assist for their third on 37 minutes when Almeida reacted quickest to prod past Forde after he had kept out the Real Madrid star's close-range header.
James McClean pulled a goal back for Martin O'Neill's side after the break, beating Rui Patricio after a mazy run, but Portugal added further goals in the closing minutes from Vieirinha and Coentrao.
And Nani was delighted to see his old Manchester United team-mate back in action, saying: "I think he showed he's good, he's well, and I think he showed he will be 100 percent.
"We are in a tough group but when you are in the World Cup you know you have to challenge the best teams. We are ready for that and we are confident."