Ayala, twice a La Liga champion with Valencia and widely regarded as one of the best in his position in Spain, faced Guardiola's Barcelona in the latter part of his career with Real Zaragoza.
The centre-back - who won 115 caps for Argentina - admits that he has never seen a finer side but feels that the Manchester City manager's methods have encouraged modern defenders to abandon what should be their primary focus.
"Guardiola's Barcelona is the best team I've seen in my life, but in a way they've been damaging," he told La Nacion.
"Now, a lot of defenders want to go out playing as if they were at Barcelona, and no, they can't do that.
"Centre-backs? Defend first, give me some security. Full-backs? Don't lose sight of that fact that, first and foremost, you are defenders."
Ayala was named in the All-Star team for the 2006 FIFA World Cup - a tournament at which Lionel Messi became Argentina's youngest goalscorer in the tournament at the age of 18 years and 357 days.
Messi has gone on to become his country's leading marksman but has faced significant criticism for failing to lead the team to a major trophy, having suffered defeat in three Copa America finals and the World Cup in 2014.
Ayala believes the Barca star has been hurt by such scrutiny but says fans should enjoy watching him in the team for as long as they can.
"I imagine that the criticism has hurt him," he said. "Even more so for a guy who has gotten better year after year and still has not been able to win anything with the national team.
"But he always wants to be there. The problem is that we fall into comparisons: today we have Leo and we don't know when a similar player is going to appear. It might be never - so enjoy him.
"If he plays badly, he'll be criticised, but we've all had a bad day.
"He has his character and his way of being and we don't have to ask him to be Diego [Maradona]. He's not Diego - he's himself."