Toxins are biologically active substances produced by all kinds of living organisms such as bacteria, fungi, plants, and animals. They present a vast diversity of molecular structures and target a wide variety of receptors linked to physiological processes. Selected during evolution to give them a disabling/lethal effect, they display finely tuned functional properties in terms of affinity and selectivity. Toxins are, therefore, very attractive compounds because they exhibit a Janus-like character, being both poisons and remedies, and, as a matter of fact, have been primarily investigated not only for the light they can throw on fundamental physiological processes, but also for their potential therapeutic applications. The Toxins Special Issue entitled “Toxins: Mr Hyde or Dr Jekyll?” will accept manuscripts describing recent advances concerning toxins of various origins (such as animal, bacterial, fungi, marine and plant toxins) and a variety of topics covering toxin structure and organization, toxin receptor/target, phylogeny, toxinogenesis regulation, medical application, toxin function/activity, and toxin delivery into cell. This Special Issue is open (but not limited) to oral communications and posters that will be presented during the virtual meeting of the French Society of Toxinology (SFET) that will be held on 9th and 10th December 2021 (e-RT27—27th SFET meeting).