The visitors took the lead early in the game through a Gomaa Mashour penalty.
But Al-Gaish's hopes of maintaining their advantage were dealt a major blow after Hassan Awad and Ibrahim Al-Shayeb were sent off in the space of five second-half minutes.
Ismaili soon capitalized on their numerical advantage as Sherif Abdul-Fadil, who received his marching orders later on, leveled the score.
Youssef Gamal put the Dervishes ahead as the hosts looked on their way to a comfortable win.
Two goals from Abdullah Al-Saied and substitute Mostafa Karim ensured Ismaili would claim all three points.
Mashour struck home from another penalty in the dying seconds but his goal proved just a consolation.
Ismaili climbed to second place in the Egyptian League table with 50 points, ahead of third-placed Zamalek on goal difference. Al-Gaish are third on 47 points.
Zamalek, Ismaili and Al-Gaish compete for the second spot which brings with it CAF Champions League qualification.
Early Lead
Mashour stunned the home crowd after ten minutes when he converted a penalty after Abdul-Fadil handled the ball inside the area.
Ismaili had to thank keeper Mohamed Sobhi for keeping the deficit as it is after he blocked two powerful shots from Ernest Papa Arko and Mamdouh Abdul-Hai.
At the other end, Mohamed Fadl had a goal wrongly ruled out for offside and Saied squandered a glorious opportunity when he went one-on-one with the keeper.
Ismaili coach Emad Soliman introduced Iraqi striker Karim instead of defender Ahmed Khairi in a bid to increase his attacking options.
Abdul-Fadil came close to scoring the equalizer but his header from Mohamed Hommos' corner narrowly missed the target.
Turning Point
Awad and Al-Shayeb were sent off for second bookable offenses in the 55 and 60 minutes respectively.
Ismaili took advantage shortly after when Abdul-Fadil's powerful low bullet went into the bottom corner two minutes past the hour mark.
The two-time Egyptian champions went ahead eight minutes later through Gamal, who came off the bench in the second half.
Gamal collected Fadl's superb back-heel inside the area before chipping over Al-Gaish guardian.
Saied added the third one minute from time with a delightful curling effort from inside the area.
Karim successfully rounded off a swift counter attack to complete the rout as Mahsour's late penalty was not enough for Al-Gaish.