This either speaks literally of supernatural protection if we pick up a snake, or symbolically of protection in our fight against the devil. Since the other four signs in this list are literal, it is most probable that this means physically taking up snakes.
The apostle Paul experienced this supernatural protection from a viper when he was shipwrecked on the island of Melita (Acts 28:3-5). However, this is the only recorded example of this type of protection in the New Testament.
There is no record of the disciples picking up snakes just to prove they were believers. That would be tempting God (Lk. 4:9-12). This, as well as drinking any deadly thing, is a promise that if we pick up snakes accidentally or are forced into that position because of our stand for Christ, we can believe for supernatural protection.
The power that is now working in believers is the same power that worked in Christ to raise Him from the dead. Everything we have as believers in Christ comes from our union with Him. Therefore, what is true of Him is true of us too. We have come to share in Christ’s throne, to partake in the authority that the throne represents, and to exercise divine power and dominion. There is no place in the New Testament that tells us to ask God to do something about the devil. Rather, we, (the church) are told to do something about the devil. This is because we have been given delegated authority over the works of the enemy. God desires that the church be enlightened to this, and walk in victory.