Sergei Ivanov said the North Atlantic Treaty Organization (NATO) was following an aggressive strategy and treating Russia as a threat rather than a partner.
"If NATO continues to keep to its offensive military doctrine, then Russia's military planning and the principles of Russia's military procurement -- including in the nuclear sphere -- will be adequately reevaluated," the Interfax new agency quoted Ivanov as saying.
"Russia is carefully observing the process of NATO's transformation," said Ivanov, who is seen as one of President Vladimir Putin's closest political allies in government.
He said that some new NATO members both "directly and indirectly" display anti-Russian policies.
Russia and NATO have recently come to blows over the alliance's plans to station warplanes in the three Baltic states and former Soviet republics of Estonia, Latvia and Lithuania.
All are due to formally join NATO on April 2. Russia had spent years fruitlessly trying to avert the expansion up to its borders and is growing increasingly concerned that the warplanes stationed in the Baltic region will spy on its defenses.
The State Duma lower house of parliament spent the day Thursday drafting a tough new resolution to be issued on the day of the expansion while senior diplomats said they mostly feared that NATO would only continue to grow.
"The majority of the population of our country sees NATO expansion as a threat to Russia," the Duma's security committee chief Vladimir Vasilyev told Interfax.
Meanwhile Deputy Foreign Minister Vladimir Chizhov said Russia was concerned because "this is not the first and obviously not the last wave."
The Russian defense minister's tough comments on potential nuclear weapons expansion Thursday are almost exactly the same that he made on October 2 in remarks that startled Western nations.
Russia and the United States signed a nuclear disarmament treaty in May 2002 aimed at slashing the size of the two country's "operationally deployed" arsenals by two-thirds over 10 years -- a deal aimed at sealing a new friendship between the two Cold War era foes.
But a senior US administration official said in Washington this week that the United States may use a loophole in the treaty to keep an unlimited number of warheads in storage.
And Ivanov has made repeated comments in recent months suggesting that Russia could be ready to reevaluate its own stance on that deal.
"Should NATO remain a military alliance with its current offensive military strategy, this will prompt a fundamental reassessment of Russia's military planning and arms procurement," said an internal document released by Russia's defense ministry in October.
Ivanov also reaffirmed his vow from that day that Russia reserved the right to preemptive strikes against other nations if it felt its security was under threat.
"We cannot absolutely rule out the use of preemptive force, if this serves either Russia's interests or is required by its obligations to allies."