The alleged incident at London Stadium is said to have taken place after Michail Antonio had equalised 21 minutes into the semi-final first-leg tie.
German outlet Bild reported during the match that the commentators, who were working for ARD, had their headsets ripped off and were punched several times.
West Ham believes it has found those responsible and has threatened the pair with lifetime bans if found guilty.
"In line with our zero-tolerance approach, the offenders' details have been passed onto the police, who will now conduct their own investigation," a West Ham spokesperson said.
"If the offenders are found guilty, they will be given an indefinite ban and not be permitted to enter London Stadium, nor travel with the club.
"Behaviour of this kind is unacceptable and will not be tolerated at West Ham United."
Frankfurt won the game 2-1 in London thanks to goals from Ansgar Knauff and Daichi Kamada either side of Antonio's close-range finish.
The return leg takes place at Deutsche Bank Park next Friday (AEST), with the winner to face either RB Leipzig or Rangers in next month's final in Seville.