The 11-year-old lioness passed away on Thursday after suffering from illness since August, the Ministry of Environment, Forest and Climate Change said on Thursday.
The animal was found carrying a fluid-filled growth on its belly, according to the ministry.
It had been receiving treatment from the park's veterinarian in consultation with Dr ABM Shaheed Ullah, former curator of Mirpur national zoo, and Prof Dr Rafiqul Alam, director of the Surgery and Obstetrics Department of Veterinary Teaching Hospital under Bangladesh Agricultural University.
Later, the lioness developed other physical complications, including pain in her left leg, bleeding from her mouth and breathing problems.
She started shivering on Wednesday afternoon. Desperate efforts to save her life proved futile, and the lioness was found dead on Thursday.
Earlier, 11 zebras and a tiger died at the park between Jan 2 and Jan 29 under a cloud of mystery, stirring widespread speculation.
The park authorities attributed the zebras' deaths to a combination of a bacterial outbreak and fights among themselves.
But the ministry later formed a five-strong panel to further investigate the cause of deaths and recommend the next steps.
Meanwhile, the local MP Iqbal Hossain Sabuj recently alleged that the zebras had been "killed" by safari park officials "due to internal conflicts".
Neither the park authorities nor the ministry has commented on the allegations so far.
On Jan 31, Assistant Forest Conservator Tabibur Rahman and Safari Park Veterinary Officer Hatem Sajjad Md Zulkarnain were removed from the park for the sake of a proper investigation.
Zahidul Kabir, the park's project director, has also been relieved of his post and replaced by Mollah Rezaul Karim, the forest conservator of Dhaka.