The world governing body this week confirmed its wish to expand the World Cup finals to a 48-team competition, comprising 16 groups of three.
Guardiola, 45, says adding games to a busy schedule will "kill the players".
"They are focusing on more and more and more - it affects the quality," the Spaniard added.
"I am thinking just for the players. They need to breathe, to [have a] break, to enjoy.
"It's just three substitutions now - why can you not make four, five or six? All the players [would be] involved more than before, the coaches can use different tactics."
Guardiola says increasing the number of substitutes available would lead to fewer injuries and more open games.
"Everything would be better," he said.
A decision on whether to expand the World Cup will be made in January and any change would be unlikely to take effect before 2026, but Guardiola is unconvinced by the idea.
"This kind of thing is impossible because we are going to finish [the season], then after one week the World Cup then after three weeks we go to the pre-season, we go to China, the States, Australia," he said.
"You play against Milan, Juventus, Madrid and you have to win. People demand you have to play good [with] no preparation. Then you come back and it's 11 months again and it's the European Cup."
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Manchester City boss Pep Guardiola says Fifa should consider allowing "four, five or six" substitutes to combat the threat of burnout among players.