Ryan and his outclassed teammates were on the wrong end of a shock 7-0 thrashing in the first leg of their semi-final at Camp Nou.
Luis Suarez helped himself to four goals and Lionel Messi grabbed a hat-trick in what Barca coach Luis Enrique described as a "complete performance".
Ryan was left exposed by Valencia's defenders who could not cope with Barca's dreaded attack that is widely regarded as he best in the world.
After working hard to attain full fitness following knee surgery and regain his spot in the team, the Socceroos goalkeeper said he was looking forward to the challenge of facing Suarez, Messi and Neymar in their own backyard but he now will see this as the most disastrous night of his career.
Wilkinson played alongside Ryan at Central Coast Mariners and the two were part of the team that lost to Brisbane Roar in the 2011 A-League grand final.
Wilkinson is convinced Ryan will get over the terrible ordeal and become a better person for it.
"I know Maty very well and no doubt he will be devastated," said Wilkinson, who is clubless after completing his contract with Jeonbuk Motors in the Korea Republic.
"He is one of the most competitive guys I know so that result would have hurt him.
"He will be so determined to put that result right that he will go back to training and work harder and harder to get better. That's what he is like.
"Mentally he will be fine and he will bounce back, no problem."
Wilkinson said he had no doubt that Ryan will put the humbling result behind him and shift his focus on Valencia's immediate future.
"Sometimes in football the results happen and you need to take what you can from the game and move on as quickly as possible," Wilkinson said.
"He will be looking forward to the next game and getting back out there.
"He is a confident guy and the result in Barcelona won't change that, I can tell you."
Sainsbury won the 2013 A-League grand final and the 2015 AFC Asian Cup with Ryan and has just signed for Chinese club Jiangsu Suning.
The centre-back echoed Wilkinson's sentiments.
"Maty is a strong-minded person and his mentality after a loss like that will be to work harder to get better," Sainsbury said.
"He played against the best strike force of all time and it shows the level he is competing at.
"He will put it behind him and focus on the next match."
Valencia's next fixture is a league match against Real Betis in Seville on Monday (AEDT).
