Objective: To perform a comparative analysis of the clinical efficacy, mechanisms of action, and level of evidence of two tissue-oxygenation-modulating methods—ozone therapy and hyperbaric oxygen therapy (HBOT)—in the context of their application in aesthetic medicine.

Materials and Methods: A systematic search and analysis of scientific literature were conducted using the PubMed, Scopus, Web of Science, eLibrary, and CyberLeninka databases for the period 2018–2024. A total of 48 publications met the inclusion criteria, 81% of which were published within the last five years. Randomized controlled trials (RCTs), cohort studies, clinical case series, systematic reviews, and meta-analyses were included.

Results: Despite the shared objective of improving tissue trophism, ozone therapy and HBOT were found to differ fundamentally in their mechanisms of action. Ozone therapy, acting through pharmacological hormesis, is most effective for the local correction of acne, fine wrinkles, post-acne scars, and, in the form of ozone sclerotherapy, telangiectasias (CEAP class C1). Hyperbaric oxygen therapy, by providing physical hyperoxygenation, demonstrates the highest level of evidence in postoperative rehabilitation following plastic surgery, in the treatment of chronic wounds and complications, and also shows potential in systemic anti-aging therapy. The evidence base for HBOT is more robust, particularly in surgical practice, whereas further standardized RCTs are required for a number of ozone therapy indications.