Simple Summary Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. Although in the case of low-grade lesions the conventional approach is watchful waiting, some infections may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. In this context, Papilocare(& REG;) is a vaginal gel that combines components with moisturizing, tissue regeneration, and microbiota-balancing properties with ingredients that have positive effects on HPV-dependent cervical lesions and HPV clearance. According to the results obtained in this observational study with real-world data, most participants repaired their cervical lesions and cleared HPV through Papilocare(& REG;) treatment, with a good treatment tolerability, adherence, and satisfaction rates, regardless of being infected with high-risk HPV, age over 40 years or both of them. Data reported in this study strengthen the role of the vaginal gel Papilocare(& REG;) as a complementary action to the simple watchful waiting approach in HPV-related low-grade cervical lesions management. Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare(& REG;)) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women & GE; 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild-moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare(& REG;) vaginal gel than spontaneous regression rates reported in the literature.