In the aftermath of Godzilla’s attack on Tokyo and his subsequent inprisonment at Mt. Mihara, a team of scientists discovers cells left in the rubble by the monster and collects them. A group of American militants takes a sample of their own. They attempt to escape with them, but are killed by a lone assassin codenamed SSS9, who steals the sample and departs. He boards a cruise liner and heads to the Republic of Saradia to deliver the cells to the Saradia Institute of Technology and Science. The president of the institute wants to use the cells to merge with genetically-modified plants, hoping to transform Saradia’s deserts to vast greenery and end the country’s dependence on oil wells for wealth. Dr. Genshiro Shiragami and his daughter, Erika, are enlisted to aid with the ambitious project. However, a terrorist bombing destroys the institute’s laboratory, ruining the cells and killing Erika.
Five years later, Shiragami has returned to Japan and has merged some of Erika’s cells with those of a rose. He hopes to have Erika’s soul continue living in the plant. Psychic Miki Saegusa, who heads an institution for intuitive children, aids him in his research. The JSDF are using the Godzilla cells they collected to create “Anti-Nuclear Energy Bacteria”, hoping it can serve as a fatal weapon against Godzilla should he return. Scientist Kazuhito Kirishima and Lt. Goro Gondo are assigned to lead the project. They attempt to recruit Shiragami to aid them, but a mournful Shiragami declines. International tensions are increasing over the Godzilla cells: an American biological corporation called Bio-Major wants the cells for its own personal gains, as does the Saradia Institute of Technology and Science. Bio-Major sends two agents to Japan, while Saradia sends SSS9. An explosion from Mt. Mihara causes tremors across the area, including Shiragami’s home. The roses are badly damaged, and Shiragami realizes he needs a drastic plan to save Erika’s soul. He agrees to join the JSDF’s effort, giving him access to the Godzilla cells. He merges them with the roses at his lab. A night later, Bio-Major breaks into Shiragami’s lab to steal the cells, but are ambushed by SSS9. A large, tentacle-like vine emerges and attacks the trio, killing a Bio-Major agent before the other two escape. The creature escapes to a nearby lake, transforming to a giant plant-like being that Shiragami names “Biollante.”
The Bio-Major agent, in a desperate attempt to procure the cells, plants explosives around Mt. Mihara and issues an ultimatum to the Diet of Japan, warning that if he does not get the cells, he will detonate the explosives and free Godzilla. Kirishima and Gondo attempt to trade, but SSS9 thwarts the attempt and runs off with the cells. The explosives go off, and Godzilla escapes. He attempts to reach the nearest power plant to replenish his supply of nuclear energy, but Biollante calls out to him. Godzilla arrives at the lake to engage Biollante in a vicious battle, and emerges as the victor. Godzilla proceeds toward the power plant at Tsuruga, but Miki uses her psychic powers to divert him toward Osaka instead. The city is quickly evacuated, and a team of militants, led by Gondo, meet Godzilla at the central district and fire rockets infused with the anti-nuclear bacteria into his body. Gondo is killed in the process, and an unaffected Godzilla leaves the city.
Kirishima recovers the cells and returns them to the JSDF. Shiragami theorizes that if Godzilla’s body temperature is increased, the bacteria should work against him. The JSDF forms microwave-emitting plates during an artificial thunderstorm, hitting Godzilla with lightning and heating up his body temperature during a battle in the mountains outside Osaka. Godzilla is only moderately affected, but Biollante arrives to engage him in battle once again. The fight ends after Godzilla fires his atomic heat ray inside Biollante’s mouth. An exhausted Godzilla collapses on the beach, and Biollante disintegrates and her spores float to the sky, forming an image of Erika amongst the stars. Shiragami, watching the scene, is shot dead by SSS9. Kirishima chases the assassin and, after a brief scuffle, SSS9 is killed by a microwave-emitting plate. Godzilla reawakens and leaves for the ocean.