Hypnosis is recognized as an effective non-pharmacological intervention for managing anxiety, pain, and physiological stress during invasive medical procedures. Despite its growing use, variability in techniques and inconsistent outcome measurements have challenged its clinical standardization. This systematic review and meta-analysis evaluated the effectiveness of hypnosis in reducing anxiety, pain, and physiological stress during invasive procedures, while identifying the most effective techniques as well as assessing analgesic use and safety. A comprehensive literature search was conducted in PubMed, Cochrane Library, and Scopus to identify randomized controlled trials (RCTs) evaluating hypnosis in invasive procedures. Eligible studies were assessed for bias using the Revised Cochrane Risk of Bias Tool. Meta-analyses were performed with a random-effects model, and subgroup analyses were conducted based on hypnosis techniques, patient characteristics, and procedure types. Twenty RCTs with 1250 patients were included. Hypnosis significantly reduced anxiety (SMD = −0.43, 95 % CI: −0.58 to −0.28, p < 0.001) and pain (SMD = −0.35, 95 % CI: −0.50 to −0.20, p < 0.001) compared to standard care. Subgroup analyses indicated that virtual reality-enhanced hypnosis and tailored interventions for high-anxiety procedures were most beneficial. Physiological stress markers, including heart rate and blood pressure, were also reduced, supporting the calming effects of hypnosis. Adverse effects were minimal. Hypnosis is effective and safe for reducing anxiety and pain during invasive medical procedures. Standardized protocols and further research are needed to optimize its clinical use and enhance adoption in routine care.