This forum can’t explain why Jesus’ apparent ‘guaranteed protection’ is limited to some forms of harm and not others, nor can it explain why our contemporary experience of ‘signs and wonders’ is so different from the New Testament stories. Those are theological questions far outside the parameters of hermeneutics. But we can look at the text and discern how it was likely intended by the author and the readers who passed it on to us ... even if that leaves us with questions about the applicability of the text today.
The immediate context of Mk.16:18 is Jesus’ commissioning of the 11 disciples following his resurrection:
15 And He said to them, “Go into all the world and preach the gospel
to all creation. 16 He who has believed and has been baptized shall
be saved; but he who has disbelieved shall be condemned. 17 These
signs will accompany those who have believed: in My name they will cast out demons, they will speak with new tongues; 18 they will pick up serpents, and if they drink any deadly poison, it will not hurt them; they will lay hands on the sick, and they will recover.”
After Jesus spoke to them, “He was received up into heaven” (v.19), and the disciples “went out and preached everywhere, while the Lord worked with them, and confirmed the word by the signs that followed” (v.20, NASB).
This passage varies in detail but shares several motifs with the other synoptic gospels, especially Mt.28:16-20 (of which many scholars think this a later expansion). Miraculous signs (σημεῖον, sēmeion) are described throughout the New Testament, including exorcisms (e.g. Acts 8:6-7; 16:18; 19:11-20), speaking in tongues (e.g. Acts 2:4-11; 10:46; 19:6), and healings (e.g. Acts 3:1-9; 5:16). While handling snakes and drinking poison unharmed have no NT parallels (NOAB, v.18 note), church tradition includes stories of these among the signs accompanying the gospel in its early years as well.
Snakes: Though Jesus gave the disciples “authority to tread on serpents and scorpions” (Lk.10:19), and Paul was unharmed when bitten by a viper on Melita (Acts 28:1-6), there is no biblical instance of ‘taking up’ snakes in the sense of actually handling them as suggested in this verse. But there is a curious textual issue: some manuscripts seem to have replaced the καιναῖς (the ‘new’ related to tongues) with καὶ ἐν ταῖς χερσίν, making the reading “and in their hands they will take up snakes.” This fuller phrasing is reflected in the NIV, ESV, and NRSV, for example, and leads some commentators (e.g. Barnes) to see Paul’s viper bite as a ‘fulfillment’ of this verse. Meyer, however, called the inserted phrase “too feebly attested ... an exegetical addition,” and it does not appear in the KJV or NASB, among others. Jamieson-Fausset-Brown and Meyer saw no example of snake handling in the New Testament at all.
Poison: Likewise for the drinking of ‘deadly’ things: “Of this there is no recorded instance in the New Testament,” wrote Ellicott. But, he added, “it finds an illustration in the tradition of the poisoned cup which was offered to St. John.” According to Meyer, the story of John surviving a ‘poison-draught’ (hemlock, according to the Cambridge Bible Commentary) is a case of a legend arising to satisfy Jesus’ prophesy in Mt.20:23 (“You will indeed drink My cup”). Papias told the same poison survival story of Joseph (Justus) Barsabas, the disciple who lost the ‘casting of lots’ to Matthias to replace Judas Iscariot as one of the 12 (Euseb. H.E.iii.39). Christian tradition says Justus went on to became a bishop and died a martyr (though apparently not by poisoning).
Whatever the historicity of these traditions – and however dubious the authenticity of this ‘long ending’ of Mark’s gospel – the most obvious reading of the text itself is its plain, literal meaning. While Jesus used ‘brood of vipers’ as a rhetorical put-down, and James wrote metaphorically of the tongue being full of ‘deadly poison’ (Jas.3:38), there is no hint in the text that this author intended snakes and poisons – or any of the five ‘signs’ – to mask a hidden figurative or ‘spiritual’ interpretation. Consistent with the characteristics of kerygmatic ‘biography’ (which are well worth exploring), the author seems to have intended these last words of Jesus to his disciples quite literally.
And according to tradition, early Christians believed the words were confirmed "by the signs that followed" (v.20). How we understand their testimony today is a question of theology, not hermeneutics.