Ronaldo was named among the substitutes during Man United's trip to the Etihad Stadium, but he did not feature even when the visitors looked for an avenue back into the match.
Keane told Sky Sports: "I think Man United are showing disrespect to Ronaldo. I think he should have been let go before the [closing] of the window.
"Okay, you're the manager, you need options but you don't hold onto Ronaldo to sit on the bench. He's one of the greatest players ever.
"He's played him in one or two European games. It's just going to get uglier as the season goes on.
"If he's sitting on the bench for United, week in, week out it's just going to get uglier. I think United have shown nothing but disrespect to Ronaldo.
"They should have let him go when the opportunity came. He did have options, I know that for a fact.
"But to hold onto Ronaldo to sit on the bench, I think is ridiculous for a player of his stature."
The former Red Devils captain added: "So what if you're 4-0 down. You look at his goal record, as good a chance of anyone of putting it in the back of the net.
"People are obsessed with the pressing side of the game. You put the balls in the right areas, he'll score goals."
Keane was also asked whether trouble could be on the horizon at Old Trafford if Ronaldo keeps being omitted from the starting line-up. He admitted this could be the case.
Keane continued: "I think he could be [a distraction in dressing room]. I think he will be if the season goes ugly.
"Because Ronaldo, the most natural thing in the world is he's going to be frustrated. Tomorrow, he's going to be in with the other lads. That's fine, that's the deal. But it's clear you're not really going to be starting if everyone is fit. Ronaldo will not be starting.
"If there's a few injuries, of course. But Ronaldo doesn't want to be sitting there thinking: 'if there's a few injuries I might get an opportunity.'
"You see him in the warm up today, you see him on the bench. He'll be hurting badly, let me tell you, despite what he's won in the game. And he's won a few big prizes let me tell you.
"But the great players and the top players want to play week in, week out. He did not come back to United to sit on the bench in a derby game."