In the context of the menopausal transition, genitourinary syndrome of menopause (GSM) refers to a range of genitourinary symptoms, from vaginal dryness to dysuria and urinary urgency. While hormonal treatments are standard, their associated side effects have driven the exploration of alternatives like vaginal CO laser. We aimed to evaluate the randomized controlled trials (RCTs) comparing vaginal CO laser treatment for GSM to sham controls. This systematic review sourced four electronic databases until June 2023. The analysis incorporated seven RCTs with 407 women. The CO laser and sham control were comparable for most parameters, including the female sexual function index (FSFI) and visual analogue scale (VAS) for dyspareunia, vaginal health index, pH, and patient satisfaction. However, the CO laser group showed significant improvement in the vaginal assessment scale for GSM symptoms. Sensitivity analyses revealed that parameters like FSFI showed significant differences in favor of CO laser group upon the exclusion of specific studies. In conclusion, vaginal CO laser therapy emerges as a promising alternative for GSM management, especially for most bothersome GSM symptoms; however, the need for further well-designed RCTs remains to validate its broad safety and efficacy.