High-intensity focused ultrasound (HIFU) is a non-surgical and noninvasive treatment modality that depends on external ultrasound energy sources that induce focused mass ablation and protein degeneration in the treatment area via thermal energy penetration under the intact skin. We aim in our study to collectively evaluate the safety of HIFU for the treatment of different obstetric and gynecological diseases in the literature. We searched PubMed, Scopus, and Science Direct databases, without restriction on date or language, from the inception of these databases until January 20, 2024. We also examined the references of the included studies in the Mendeley archive for eligible articles. We found a total of 706 studies. After the screening and selection process, 56 participants were included. Our dichotomous outcomes were pooled in our single-arm meta-analysis as risk ratio (RR) and with 95% confidence interval (CI) while our continuous outcomes were pooled as mean change and 95% CIs. Fixed- or random-effects models were applied depending on the heterogeneity detected. Our systematic review and meta-analysis included 56 studies including 11.740 patients. Depending on the Society of Interventional Radiology (SIR) classification for adverse effects. The results of this meta-analysis for the type A category that did not require clinical intervention found that pain in the treatment site estimated RR with 95% CI: 0.61 (0.33, 0.89), abnormal vaginal discharge 0.16 (0.073, 0.24), low-grade fever (<38 °C) 0.005 (0.002, 0.009). Sensory abnormalities of the lower limbs were examined in 3390 individuals and observed in only 19 patients who experienced gradual relief of symptoms within one month after treatment. Regarding SIR type B, 99 of a total of 6.437 patients had small vesicles and superficial burns with pooled RR and 95% CI: 0.012 (0.007, 0.018). In terms of groin or perianal and lower abdominal pain, our RRs with 95% CIs were 0.1 (0.067, 0.13) and 0.38 (0.25, 0.51). However, vaginal bleeding was detected in only 32 out of a total of 3.017. Major adverse events like lumber disc herniation, thrombocytopenia, and renal failure, were unmentionable. Additionally, our included studies did not record any deaths. HIFU, either alone or in combination with oxytocin or any other enhancing agent, is safe for patients with different gynecological and obstetric diseases. In terms of efficacy, it showed promising results compared with traditional treatment lines. To our knowledge, we are the first and most comprehensive meta-analysis in the literature that has studied the different safety outcomes related to HIFU as a treatment modality for different obstetric and gynecological diseases with a very large sample size, making our evidence strong and less attributed to errors.