In the park where they normally meet, Suneo is bragging to Gaian and Shizuka about tickets that he has acquired for an Express Train. He tells the two of them that he only has three tickets, and it is his intention not to invite Nobita. Nobita then appears looking very worried, and asks the others whether they have seen Doraemon as he has been missing for a few days.
Nobita returns home, delighted to see that Doremon is back home. Doraemon explains that he had briefly returned to the 22nd Century and had acquired tickets for a Mystery Galactic Express Train. The train's destination is unknown, and Doremon doesn't know how long the trip will take either. After Nobita expresses concerns about missing school, Doremon reassured him that he will be able to go to school in the day and then ride the train at night by using the Dokodemo Door to travel between home and the train.
The following day, Nobita goes to school and tells his friends all about the Mystery Galactic Express Train, and invites them to come with him on the train, only to realise that it will clash with Suneo's plans. Both Gaian and Shizuka both appear to want to go with Nobita. Suneo is jealous and is angry that his friends would rather go with Nobita than with him. He warns them that space is a dangerous place, and going with Nobita would be unsafe.
Gaian and Shizuka consider what to do. They decide to go with Nobita, although Shizuka in particular feels sorry for Suneo. When the two of them turn up at Nobita's house, they're surprised to see that Suneo is there already as he has decided to come with Nobita as well.
The mysterious galactic express train is a train that has 58 carriages (but only can see 8 carriages from the outside) and has 5 rooms in each carriage. Nobita and his friends are staying in Carriage No. 7
Once the train is reaching its destination (a planet), the train separates the carriages in one another and lands on an empty spot.
Meanwhile, an evil force is planning to take over the planet with the humans together, turning the humans into parasites. A few days later, the first case of parasites has been reported when Nobita and his friends were in the Dinasour world and the dinasours (the dinasours are just robots) were acting strangely. They decided to go it to the main station in the Dinasour world but the actual controls are in the main control center in the main planet. When Nobita and his friends decides to go to the main station (in the Dinasour world) but a man said that they couldn't find contact with the main control center.
Nobita and his friends went to check what happened, they found out some smoke coming out from the main control center, this is where the first parasite case was reported. When Gian and Suneo are in the main control center, investigating what happened, Suneo was captured by the parasites and has been turn into Parasite No. 0009/009
Suneo (Parasite No. 0009) trick his friends by telling them a safe place to hide, which is their own carriage, Suneo then lock them up and they couldn't get out. Then a man made Suneo faint while he was laughing evil, but he couldn't save Nobita and the others inside which the door is lock.
The driver of the train later founds out about this and decided to get the train onto another planet to be safe, but one of the parasites took half of the fuel on the train, so that the train would land in a nearby spot and they could capture the humans.
The train departed the next day but crash landed in a planet, when it turned the train upside down. As they explore the planet, they found out a nearby abandoned village which has lots of food and water for them to survive. The same man that made Suneo faint found an electronic cave map but the driver said it was useless. Gian heard the conversation and used the cave map to explore caves, but end up he got lost.
Shizuka found a weakness for the parasites turning them back into humans, they decided to use it on Suneo. Meanwhile, Doraemon and Nobita were delivering food to Suneo but Nobita got captured as a parasite but was recovered later. Suneo later got recovered and turn back to human form minutes later.
But then, they found out that Gian is missing, then they found his footprints. Meanwhile, Gian meet up with 2 people about the same age as his but don't know the way out, with no luck, the cave entrance got buried. But they managed to find a train station and a train, with luck, the train managed to get out of the mountain and Nobita and his friends were overjoyed.
They attached the train that Gian found into the mysterious galactic express train. But when they were preparing to leave, the parasites group found them and attacked them, but the humans won and all the parasites were turned back into humans again.
The end of the movie ended with Nobita and his friends bid farewell to the new friends they met in the train.