The Cross & Self-Destruction
The Son of God promises, in our main study verse, that God sent Him so that whoever believes in Him would not "perish" but have eternal life.
16For God so loved the world, that he gave his one and only Son, that whoever believes in him should not perish, but have eternal life. John 3:16
This word perish ("lost" in many other verses) is in the middle voice, as it is in many other instances when talking about people perishing. It and "have [eternal life]" are subjunctives, meaning they are conditional (i.e., it may happen, it may not).
The ones believing in Him may not destroy, ruin or lose themselves, but rather may have ageless life. For we know from His other promises that whoever ruins or loses his soul for the sake of Jesus will find it forever. And we know that Christ came not to destroy men's souls but to save them—for this is why He was sent (Matthew 18:11)! But that will be studied elsewhere.
The Cross of Christ
Notice that Christ's promise to those believing in Him has a conditional statement—they "may" not destroy themselves but may have eternal life instead. Those who do not believe are not capable of leaving that condition of self-destruction, as revealed by Paul:
18For the word of the cross is foolishness to those who are dying, but to us who are saved it is the power of God. 1 Corinthians 1:18
To the ones "destroying themselves" the word of the Cross is truly foolishness. Why specifically "the Cross?" Because it embodies what Jesus did—He died for our sins, that we might die with Him. They cannot accept that Christ has come to give them life through His and their death on the Cross. Why is this so? Paul reveals it to the Thessalonians.
Rejection of the Truth & Self-Destruction
10and with all deception of wickedness for those who are being lost, because they didn’t receive the love of the truth, that they might be saved. 2 Thessalonians 2:10
The Lawless One, the anti-Christ, will come and do great signs and wonders, with all deception of wickedness for "those being lost." Why are they being lost? "They didn't deceive the love of the truth that they might be saved." Rather, they glory in unrighteousness, and don't believe the truth, so that God then sends them a working of error, so that they believe the lie.
11Because of this, God sends them a working of error, that they should believe a lie; 12that they all might be judged who didn’t believe the truth, but had pleasure in unrighteousness. 2 Thessalonians 2:11-12
As Paul says, it is deception of wickedness—they think they have what is good but they don't realize where it leads, much as Eve in the Garden of Eden when confronted by the deception of the Serpent:
12There is a way which seems right to a man, but in the end it leads to death. Proverbs 14:12
How does all of this go together? Underlying people's self-destruction is their heart's state—they hate the truth but love and take pleasure in unrighteousness.
As mentioned elsewhere on this site, truth and righteousness are closely related in scripture, just as are untruth and unrighteousness. What is right is what is real. Those who reject what is real, true and right are those who reject Yahweh, the Author of Truth and Reality. The lifestyle that flows from such a rejection is self-destruction and God accomodates them by giving them more of what they follow after—the lie and its fruit, death.
But thanks be to our God and Father, Yahweh, Who has sent His Son so we might escape this and rather obtain Life! The Lord Jesus Christ is our rescue from that vain lifestyle that prizes unreality, unrighteousness, a rejection of the truth as revealed by the Creator.
14As Moses lifted up the serpent in the wilderness, even so must the Son of Man be lifted up, 15that whoever believes in him should not perish, but have eternal life. 16For God so loved the world, that he gave his one and only Son, that whoever believes in him should not perish, but have eternal life. John 3:14-16
Truly, this Word of the Cross is our exit from self-destruction—it remains foolishness to those who continue in their own self-ruin, but it is the glory of God for us who are believing, as Christ promised. For whoever believes in Him may not cause himself to perish but rather may have eternal life! HalleluYah!