Both goalkeepers were kept busy in an entertaining goalless draw which at least ended Mainz's three-game losing streak, although it leaves them five points adrift of the top six.
The point takes Frankfurt above Freiburg into fifth and still on course for a place in Europe next season.
Oka Nikolov was Frankfurt's hero against Schalke a week ago and the 38-year-old showed no indication that he was going to be beaten this time either as he convincingly grasped Bo Svensson's second-minute effort.
He was beaten by Nicolai Muller in the 24th minute, but the Mainz midfielder's shot also fell the wrong side of the post.
Frankfurt were not only defending, though, and Alexander Meier, back in the side after injury, forced a fine save out of Christian Wetklo at the other end just before half time.
Andreas Ivanschitz saw his goal ruled out for offside early in the second half as Mainz started to gain the upper hand.
The Austrian then sent in a cross which Zdenek Pospech headed towards goal, but Nikolov plucked the ball out of the air.
Wetklo prevented Sebastian Rode from giving Frankfurt the lead in the 82nd minute as Frankfurt responded late on.
A cross from Constant Djakpa almost found Olivier Occean in the six-yard box as Wetklo's goal started to come under more of a threat, but there was ultimately nothing between the local rivals, who had to settle for a draw.