This chapter addresses, in an integrated manner, the systemic risks of phenol-croton oil peel. Phenol exhibits high cutaneous absorption and rapid distribution, with predominantly hepatic metabolism (conjugation) and renal elimination; the severity of adverse events is mainly related to the treated area, application speed, and the patient’s clinical status. Manifestations include neurotoxicity (lethargy, seizures, coma), cardiotoxicity (arrhythmias, hypotension), respiratory toxicity (pulmonary edema, tracheobronchial inflammation), hepatotoxicity and nephrotoxicity (up to acute renal failure), as well as hematological disturbances (acidosis, methemoglobinemia, hemolysis). Clinical evidence shows that rapid and extensive applications increase the risk of arrhythmias; safe protocols emphasize multiparametric monitoring, hydration, segmented application with pauses, and a well-ventilated environment. Croton tiglium oil, rich in phorbol esters, has a potent pro-inflammatory action via protein kinase C, and may produce intense local effects and, when misused (dose/vehicle/route), adverse systemic effects; there are historical reports of severe poisoning following oral ingestion. The phytochemical variability and instability of the raw material require rigorous quality control. Collectively, the data reinforce that the therapeutic margin is narrow and that the aesthetic benefits of phenol-croton oil peels depend on pharmacokinetic knowledge, safety protocols, and exclusive medical execution.