Ronaldo was hit with a five-match ban by the Royal Spanish Football Federation (RFEF) after he pushed referee Ricardo de Burgos in the aftermath of being sent off in Sunday's opening leg.
Madrid will present their appeal case to the governing body on Wednesday morning, with Barca visiting the Santiago Bernabeu in the hope of overturning a 3-1 deficit that evening.
Zidane has studiously avoided being dragged into El Clasico politics since succeeding Rafael Benitez as Madrid boss but told a pre-match news conference "something is up" with the punishment meted out to Ronaldo, who was booked for removing his shirt in celebration of a stunning goal and dismissed for simulation.
"What we're going to do is wait for tomorrow. The committee is going to meet in the morning. After that we will see what we're going to do," Zidane said.
"I'm disappointed. All of us are disappointed. As always, I'm not going to get involved with the referees but, when you see everything that happened…
"We are going to talk to the committee about this as well. When you think he is not going to play in five games for us, something is up.
"It bothers me and it bothers all of us. It's a lot of games for him and that's all I'll say."
Pressed to clarify his remarks, Zidane said: "I've been very clear in my answer. What happened, happened. When you study it, at the end of the day, you say they have given Cristiano five matches and that's a lot.
"I hope the committee look at it. But it bothers me, when I see five matches and what [punishment] they want to give him it bothers me.
"Cristiano wants to play. When he doesn't play he's not happy."
Asked whether there was a sense of external forces in Spanish football conspiring against Ronaldo, who is currently the subject of a legal case regarding alleged tax fraud, Zidane added: "I don't know. I don't think so, I hope not.
"I hope people are conscious of the decisions they make and conscious of the jobs they do but, in the end, five games… it's not worth five games."