Former Valencia goal-poacher Villa, who joined Barcelona in 2010 in a big-money transfer, enjoyed a brilliant first term with the Catalan giants last season, culminating in his side's La Liga and Champions League triumph.
However, Spain's record goal scorer has found the going tough this campaign, having been regularly benched by manager Pep Guardiola.
Coupled with the summer marquee signings of Cesc Fabregas and Alexis Sanchez, former honcho Valdano maintained that Villa's time at Barcelona could slowly draw to a close unless he is picked against Madrid at the Santiago Bernabeu.
"It would not surprise me if Barcelona played Alexis (instead of Villa), who has found the net of late," the Argentine told Marca.
"This game is key; if he is not selected it could condemn Villa to a secondary role, and he does not deserve this."
"There are also players like Pedro who have put in superb performances against Madrid in the past."
"I hope Ozil will play. In Barcelona, Lassana Diarra would be more likely to feature, but at the Bernabeu, and with this euphoria, I think the German will play," the 56-year-old continued.
Valdano also remarked that Madrid chief Jose Mourinho's recent penchant for complaining against refereeing decisions in their recent El-Clasico fixtures will have to be clamped down.
"Talking about referees is something aesthetically deplorable in Madrid. The club cannot play that game ever again," he concluded.
Barcelon are trailing Madrid by three points going into Saturday's mouth-watering clash, with Madrid having the added advantage of a game in hand.