The Dutch started with only five first-team regulars after coach Bert van Marwijk said the match would be the last test before he reduces his 27-man squad to 23 on Thursday.
The Dutch were without Arjen Robben, Mark van Bommel and Wesley Sneijder, who all featured in Saturday's Champions League final.
The Dutch made a bright start and created chances before Van Persie opened the scoring from Van der Vaart's crossfield pass and the Arsenal forward added a second three minutes before the interval.
"We showed some fine combination football in the first half, though followed by a lesser second but for a first friendly match we can be satisfied," Van Persie told SBS6-TV.
"Van Persie was excellent tonight with two beautiful goals, but we missed the power in the second half and allowed Mexico to play much better," he said.
"But that all has to do with the intensive training sessions last days."
