Giovani was introduced for the final 20 minutes at the Rose Bowl, with Jonathan playing the final half-hour.
While their fitness gave Mexico a boost, neither could provide a breakthrough for the hosts.
Mexico had the better of the encounter, but struggled in the attacking third, while Wayne Hennessey made several decent saves to see Wales earn a draw.
World Cup places were still up for grabs for Mexico after Juan Carlos Osorio named an initial preliminary squad.
Hugo Ayala and Oswaldo Alanis formed their centre-back pairing, while Javier Hernandez started up front.
For Ryan Giggs' Wales, who failed to qualify for the World Cup, Premier League duo Ashley Williams and Aaron Ramsey were in the starting XI, but the former was substituted in the first half due to injury.
Both teams started brightly in California, with Jesus Corona forcing Hennessey into a diving save from 25 yards in the opening stages.
Mexico controlled play after an even start and went close to an opener midway through the first half, but Hennessey denied Javier Aquino in a one-on-one.
At the other end, Wales almost struck through Harry Wilson, but the Liverpool attacker curled his effort just wide after cutting inside from the right.
Hennessey was again called into action to keep the visitors level approaching half-time, the Crystal Palace goalkeeper tipping over a Hector Herrera strike.
Mexico – who face Germany, Sweden and South Korea in Group F in Russia – continued to struggle in the attacking third, Herrera's poor touch on the penalty spot costing him a chance at a shot on goal before the hour-mark.
Jonathan and Giovani dos Santos came off the bench as Mexico continued to search for a breakthrough, but they kept breaking down in the attacking third throughout the second half.
Giovani almost scored the winner in the closing stages, but Hennessey came to Wales' rescue once more.