In an appearance on CNN's "State of the Union" with Jake Tapper, the Vermont independent said the key to ousting Syrian President Bashar al-Assad was to forgo unilateral action and instead convince Russia and Iran to withdraw their support for the dictator at the heart of the more than six-year-long war.
"Assad has got to go. ISIS has got to be defeated," Sanders said. "But I do not want to see the United States get sucked into perpetual warfare in the Middle East, see our men and women get killed, trillions of dollars being spent."
The senator who ran unsuccessfully in last year's Democratic presidential primary brought up the US military's ongoing presence in Afghanistan and Iraq, saying the US could be "dragged into another war" to the detriment of domestic priorities.
"We have got to start paying attention to the needs back home," Sanders said. "The war in Iraq was the worst blunder in the modern history of this country -- precipitated mass instability. We cannot continue to make those mistakes."
President Donald Trump greenlit a cruise missile strike earlier this month on an Assad airbase after the US said the Syrian president used chemical weapons to slaughter civilians. Many politicians on both sides of the aisle hailed Trump's action.
Asked about support for the strike from within the Democratic Party and even former Obama administration officials, Sanders said the Syria strike, as well as the US dropping
one of its largest non-nuclear bombs in Afghanistan, were ineffective for problems that required a multilateral, diplomatic solution.
"It's not a question of one strike or one big bomb in Afghanistan," Sanders said. "What you need is a strategy. ... This will require intensive negotiations to tell Russia that they cannot support a dictator who is destroying his entire country. One strike is not going to do very much in that process."
Meanwhile, Sanders said he believed Trump understood he needed to work with China to rein in the North Korean nuclear threat.
"The United States must not act impulsively, and we must not act unilaterally," Sanders said.
Trump met with Chinese President Xi Jinping in the US earlier this month and spoke by phone with him last week to discuss North Korea's progress in missile development and another potential nuclear test.
Both Sanders and Trump have said the focus on the issue must remain on China. In recent days, China has signaled a possible shift on North Korea, including an editorial in Chinese media warning China could support UN sanctions on oil shipments to the isolated nation.
However, Sanders did not credit Trump with the possible progress, saying it was part of a trend.
"I think this policy shift on the part of China has been taking place for quite a while now," Sanders said.