Mustafi has faced off against both opponents in the past, and the Germany international believes that Messi just about edges things due to his movement on and off the ball.
"Lionel Messi was my hardest opponent," he told Bild. "I played him three times with Valencia. You cannot predict him, he is small and very quick, changes his direction quite often.
"When he runs towards three opponents you can nearly be sure that he breaks through. Ronaldo is more of a striker in the box. Messi can also play good passes and make his team mates stronger. For me, he is the best player in the world."
Mustafi is not a part of Germany's 23-man squad for this month's World Cup finals.