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In the near future, weapons expert James McCullen (Christopher Eccleston) has created a nanotechnology-based weapon capable of destroying an entire city. He sold four warheads to NATO, and the U.S. Army is tasked with delivering the warheads. Duke (Channing Tatum) and Ripcord (Marlon Wayans) are delivering the warheads when they are ambushed by the Baroness (Sienna Miller). Duke and Ripcord are rescued by Scarlett (Rachel Nichols), Snake Eyes (Ray Park) and Heavy Duty (Adewale Akinnuoye-Agbaje). They take the warheads to The Pit, G.I. Joe's command center in North Africa, and upon arriving rendezvous with General Hawk (Dennis Quaid), the head of the G.I. Joe Team. Hawk takes command of the war-heads and excuses Duke and Ripcord, but when Duke reveals that he knows the Baroness, Hawk allows them to join G.I. Joe.

McCullen and his associate the Doctor (Joseph Gordon-Levitt) are revealed to be using the same nanotechnology to build an army of soldiers. McCullen plans on using the warheads to bring panic. Using a tracking device McCullen locates the G.I. Joe base and sends Storm Shadow (Lee Byung-hun) and the Baroness to retrieve the warheads. After a fight, Storm Shadow and the Baroness retrieve the warheads and take them to Baron DeCobray, the Baroness's husband, for him to weaponize. They then plan to attack the Eiffel Tower.

The G.I. Joe team tracks down the Baroness and Storm Shadow and pursue them through the streets of Paris but are unsuccessful in stopping them from launching the missile. The nano-mites eat through part of the tower before Duke hits the kill switch, but in doing so he is captured and taken to McCullen's base under the Arctic.

G.I. Joe locates the secret base and fly to the Arctic, meanwhile McCullen loads three missiles with nano-mite war-heads. Ripcord pursues the missiles while Scarlett and Snake Eyes rescue Duke.

The Doctor reveals he is Rex Lewis, the Baroness's brother believed to have been killed on a mission led by Duke four years ago. He was trapped in a bunker with Doctor Mindbender (Kevin O'Connor) and learned about the nano-technology. He was disfigured in a blast which Duke and the Baroness believed killed him. The Baroness tries to free Duke but the Doctor reveals he has implanted her with nano-mites (which explains why she turned evil; it wasn't a personal choice, she has been under her brother's control).

McCullen tries to kill Duke but he is unsuccessful and his face is burned as he flees with the Doctor to an escape vessel. Duke and the Baroness pursue him while Scarlett, Heavy Duty and Snake Eyes attempt to stop the missiles and shut down the Arctic base.

Snake Eyes destroys the first missile using his snowmobile. Ripcord takes off in a prototype jet, and destroys the second missile before it reaches Moscow. In destroying the third warhead, the jet is covered in nano-mites and he pilots it into the atmosphere, then ejects and lands in Washington DC.

The Doctor heals McCullen's burned face with nano-mites, but in doing so he encases it in silver. He declares McCullen to now be Destro, and the Doctor reveals that he himself is the new Cobra Commander. They are soon captured by G.I. Joe. In Africa the G.I. Joe team makes final preparations to decommission their North African base of operations, transferring all personnel and equipment to the supercarrier USS Flagg. Anna (back with Duke) is in custody there until they can remove the nano-mites from her body. Meanwhile, the master of disguise Zartan (Arnold Vosloo), who was surgically changed by the Doctor, infiltrates the White House and assumes the identity of the President of the United States (Jonathan Pryce).

from: wikipedia