The manager believes the risk of exacerbating the Manchester United striker's injuries was a big concern and would not have played him regardless of the game's importance
The 30-year-old withdrew from the Oranje squad, complaining of toe and groin injuries following his winning goal against his former club Arsenal on Sunday.
The Dutch face Japan and Colombia in their pair of friendly encounters, and Van Gaal says he was not going to risk further aggravating his country's record scorer's niggling problems.
"It will be different with other players this time, especially with another striker," he told reporters. "When we played Turkey, Van Persie also wasn't 100 per cent per cent, but because he's an important player, he was there anyway.
"Van Persie called me on Sunday and we discussed the situation. He didn't really have a holiday this summer, because he had to go to Asia with United. He just went on and on.
"It's smart to keep in mind what that does to a player. Even if we had an important match, I wouldn't have played him this time."
However, Van Gaal says that when the Dutch attacker is fit, his position alongside Arjen Robben and Kevin Strootman in the team is not at threat.
"It's unbelievable but true, every player is fit. I always think of players who are fit and available," he continued.
"Those are the ones I pick. RVP, [Dirk] Kuyt and Van Persie are not available, but I always said that Robben, Strootman and Van Persie are sure of their places if they are in shape.
"It will be interesting to see how we manage without Van Persie. We have to show how we are when he's not available. That could always be a scenario in Brazil."
Netherlands have already seen their attacking options curtailed with the absence of injured trio Kuyt, Ricky van Wolfswinkel and Klaas-Jan Huntelaar.
"Because Van Wolfswinkel and Huntelaar are injured, we dont have many strikers," Van Gaal said. "They are the ones behind Van Persie, but that can change if someone steps up now.
"Siem de Jong is a back-up plan in case of emergency, just like he is at Ajax.
"[Jeremain] Lens is also an option as central striker, especially when we come ahead in a match. It's nice to experience something like this so we can solve a problem."