Objective To evaluate the acceptability, tolerability, and effects on vulvovaginitis symptoms and signs of a non-soap, herbal-based intimate solution (Zelesse®). Methods We conducted a prospective, observational, multicenter study including adult women with symptoms and signs of vulvovaginitis with various etiologies, including candidiasis, trichomoniasis, bacterial vaginosis, and atrophic and irritative vaginitis. The presence and intensity of signs (edema, erythema, vaginal discharge) and symptoms (pruritus) of vulvovaginitis were evaluated before and after 5–15 days of daily use of Zelesse® alone or as a coadjuvant in antimicrobial therapy. Variables following a normal distribution and categorical variables were analyzed using the Student t-test and chi-square or Fisher’s exact test, respectively. Results A total 137 women were enrolled in the study; 87 (63.5%) women received concomitant antimicrobials and 50 (36.5%) used Zelesse® only. Global symptom scores and frequency of patients with vulvovaginitis signs and symptoms, and their mean intensity, decreased after treatment in both patient groups. Vaginal pH and (in the Zelesse®-only group) vaginal flora remained unaltered. The product was safe, well tolerated, and highly accepted by patients. Conclusions Zelesse®, the non-soap herbal-based solution in this study, may represent a safe and effective option for symptomatic relief of vulvovaginitis.