The Real Madrid star was rested for their final Euro 2016 qualifier against Serbia, with top spot in Group I already assured.
Santos has again opted to leave Ronaldo out for this month's friendly fixtures, with Ricardo Quaresma, Ricardo Carvalho and Tiago also absent.
As Adrien Silva, Danny, Eder and Fabio Coentrao miss out through injury, Santos was surprised that questions posed were mainly about Ronaldo's absence and not the players picked.
"Why only talk about Cristiano Ronaldo when there are five or six absences?" the coach said.
"Cristiano is indisputable, but this is my decision.
"For a long time it's been said we don't have players and, when I select others, I am criticised.
"In fact, Portugal has a new generation of players emerging. We have a lot of players that enable us to make this choice.
"These games are not for experimenting, all players form part of the group."
Portugal travel to face Russia a week on Saturday before playing Luxembourg three days later.
Lucas Joao, Ricardo Pereira and Goncalo Guedes could all be in line for a first senior appearance, while Nelson Oliveira has been included for the first time under Santos.
Squad in full:
Goalkeepers: Anthony Lopes (Lyon), Eduardo (Dinamo Zagreb), Rui Patricio (Sporting CP).
Defenders: Bruno Alves (Fenerbahce), Cedric (Southampton), Eliseu (Benfica), Jose Fonte (Southampton), Neto (Zenit), Pepe (Real Madrid), Raphael Guerreiro (Lorient), Vieirinha (Wolfsburg).
Midfielders: Andre Andre (Porto), Andre Gomes (Valencia), Danilo (Porto), Joao Mario (Sporting CP), Joao Moutinho (Monaco), William Carvalho (Sporting CP).
Forwards: Bernardo Silva (Monaco), Goncalo Guedes (Benfica), Lucas Joao (Sheffield Wednesday), Nani (Fenerbahce), Nelson Oliveira (Nottingham Forest), Ricardo Pereira (Nice).