The panda was put under deep anaesthesia to take CT scans and the team decided to "let Tuan Tuan continue to sleep" after the results indicated his condition was "irreversible."
A panda that China gifted to Taiwan 14 years ago as a symbol of what were then warmer ties has died after suffering a spate of seizures.
"Our medical team has confirmed that Tuan Tuan's heart stopped beating at 13:48 (0548 GMT)," Taipei Zoo said in a short statement on Saturday.
He was put under deep anaesthesia to take CT scans and the team decided to "let Tuan Tuan continue to sleep" after the results indicated his condition was "irreversible", zoo officials said.
"It would have been extremely painful and risky for Tuan Tuan to resuscitate him from the anaesthesia," said spokesman Eric Tsao.
Vets first noticed Tuan Tuan, 18, was ill in August, when he began suffering seizures and appeared increasingly unsteady and lethargic.
Scans showed he had a brain lesion and he was placed on anti-seizure medication.
The zoo suspected Tuan Tuan had a tumour and he was moved into palliative care last month. But more frequent seizures returned in the past few days and medicine could not ease the symptoms.
Tuan Tuan and his breeding mate Yuan Yuan were given to Taiwan by Beijing in late 2008, at a time when relations between the two were more cordial.
Taiwan's top China policy-making body, the Mainland Affairs Council (MAC), hailed the panda's role in improving ties with Beijing.
Tuan Tuan "let everyone know more about giant pandas and help promote exchanges between the two sides... MAC is saddened that he has passed away," it said in a statement.
The panda couple - whose names combined mean "reunion" or "unity" - had become huge stars in Taiwan and Yuan Yuan has given birth to two female cubs.
China has long deployed "panda diplomacy" and the gifting of Tuan Tuan and Yuan Yuan was seen as endorsing the presidency of then Beijing-friendly leader Ma Ying-jeou.
Relations between China and Taiwan have been on ice since 2016 with Beijing severing official communications and government visits between the two sides scrapped.
China views Taiwan as part of its territory and has vowed to one day bring the self-ruled island into the fold.