What does it mean to be “wise as serpents”?

What Jesus said at the beginning of that verse is important. It says,

“Behold, I send you forth as sheep in the midst of wolves: be ye therefore wise as serpents, and harmless as doves.” Matthew 16:10

Jesus knew that the ones he was sending out to spread the Gospel would be in physical danger from some in the world. Jesus calls them “wolves,” while his followers he characterizes as “sheep.” When he says they should be wise as serpents, he meant they should be careful in dealing with the world. The Greek word translated “”wise” means to be “discreet or “careful.” A serpent is cautious when presented with a dangerous situation. So this is Jesus’ way to remind the preachers of the Gospel to use wisdom and not put themselves in unnecessary danger.

At the same time they should be harmless, or innocent as doves. They should not return evil for evil, but simply preach the truth and cause no harm. There is great wisdom in  what Jesus said. We are not to fear the world, but at the same time, be careful of its influence and occasional desire to harm those who speak truth.