Purpose: To assess the feasibility and efficacy of a nonhormonal soy isoflavone vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women. Materials and Methods: It was a single-center, prospective study. We identified postmenopausal women having at least one of the following self-assessed moderate to severe symptoms of vulvovaginal atrophy (VVA). Participants used soy isoflavone gel (0.5%) twice weekly for 12 weeks. Vulvovaginal symptoms and pH were assessed at three time points [baseline (T1), 4 weeks (T2) and 12 weeks (T3) with clinical evaluation, the Vaginal Health Index, Vaginal Assessment Scale, and the Vulvar Assessment Scale]. Efficacy and tolerability were assessed using the Patient Global Impression of Improvement (PGI-I) Scale and adverse effects were also recorded. In the results of 95 patients, the mean age was 55 years (range, 31–78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. Vaginal Assessment Scale/Vulvar Assessment Scale scores significantly improved at all assessment points (all p = 6.5) and decreased from 26% at T1 to 19% at T3 (p = 0.18). Conclusion: Soy isoflavone vaginal gel (0.5%) use on a daily basis for 12 weeks leads to significant improvements in the symptoms of VVA in postmenopausal women. Topical isoflavones are a good treatment option for VVA, especially in women who either do not wish to use hormonal therapy or have contraindications to its use.