The efficacy of the phenol-croton oil peel results from the synergy between two agents with distinct mechanisms of action. Phenol (C6H5OH) is a protein-denaturing agent: it induces coagulative necrosis of the epidermis/superficial dermis, modulating cutaneous penetration through the formation of a protein coagulum. It has a local anesthetic effect and causes superficial vasoconstriction; nevertheless, its systemic absorption is rapid and depends mainly on the treated area, application speed, skin hydration, and hepatic-renal function. Once absorbed, it undergoes hepatic conjugation (mainly glucuronidation/sulfonation) and renal elimination, necessitating strict dose control and a segmented technique. When used alone, phenol tends to produce more superficial necrosis and limited neocollagenesis. Croton tiglium oil, rich in phorbol esters, activates protein kinase C, induces intense neutrophilic inflammation (including the formation of extracellular traps—NETosis), increases cytokine and TGF-β levels, and stimulates fibroblasts, resulting in dermal remodeling with collagen deposition (especially type III). Experimental evidence shows that the addition of croton oil deepens the injury and enhances the regenerative response compared to phenol alone. As a plant-derived matrix, it exhibits phytochemical variability and is unstable during storage, requiring standardization, analytical certification, and quality control of the raw material. An integrated understanding of physicochemical properties, pharmacology, pharmacokinetics, and safety underpins the effective and safe clinical application of the phenol-croton oil peel.