No fatalities were immediately reported but the building was fully staffed with policemen when the fire broke out before dawn.
By the time the first rescue services arrived, the blaze had engulfed the entire building of the Ismailia Security Directorate.
Flames raged through the multi-storey building that was completely obscured by a massive cloud of smoke before the blaze was brought under control.
By dawn, all that remained of the headquarters was a charred shell as emergency services carried out cooling procedures to prevent another fire from breaking out.
On social media, users shared footage of the fire which showed individuals trapped inside, calling for help from the windows.
The cause of the blaze is not yet known and security forces have sealed off the area, where AFP correspondents saw rescuers attempting to evacuate those trapped inside, assisted by a crane.
Interior Minister Mahmoud Tawfik ordered an investigation into the causes of the fire, as well as a "structural safety review" for the building, his ministry said in a statement.
Authorities have not made statements on how many policemen and detainees were inside the building overnight.
- Emergency services -
Of 26 wounded who were transferred to a local hospital, 24 had suffered from "asphyxiation" and two from burns, the health ministry reported.
Twelve more were treated at the scene.
The health ministry deployed 50 ambulances to the scene, which were joined by military emergency services including two planes, according to local media.
Deadly blazes are a common hazard in Egypt, where fire codes are rarely enforced and emergency services are often slow to arrive.
In August 2022, a fire caused by an electrical short circuit killed 41 worshippers in a Cairo church, prompting calls to improve the country's infrastructure and the response time of the fire brigade.
Most suffocated while trying to flee the building. Others jumped out of windows to escape the blaze, as firefighters took over an hour to arrive.
The disaster was blamed on the dilapidated building which housed the church, and the maze of alleyways in the neighborhood where it was located, which slowed down arriving firefighters.
Monday's fire took place in one of dozens of new police headquarters built or renovated across the country in the past decade.
In March 2021, at least 20 people died in a fire at a textile factory in the capital, while in 2020, two hospital fires killed 14 people.
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