Background: Persistent infection with human papillomavirus (HPV) is a key factor in cervical carcinogenesis. Immune-mediated mechanisms play a central role in viral clearance, leading to interest in immunomodulatory supportive therapies. Objectives: This study aimed to evaluate the association between intravaginal Aloe barbadensis use and HPV clearance in HPV-positive women. Methods: This retrospective observational study included 251 HPV-positive women aged ≥30 years. Of these, 164 received intravaginal Aloe barbadensis–containing vaginal capsules for 10 days, while 87 received no immunomodulatory treatment. HPV-PCR and cytological results were evaluated at baseline and after one year of follow-up. Results: HPV clearance was observed in 45.7% of patients in the Aloe barbadensis group and 36.8% in the control group, with no statistically significant difference between groups (p = 0.219). Subgroup analyses based on smoking status and HPV genotype also revealed no significant differences in clearance rates. Conclusion: Intravaginal Aloe barbadensis use was not associated with a statistically significant improvement in HPV clearance. The findings highlight the complexity of HPV persistence and suggest that single-agent immunomodulatory interventions may have limited clinical impact.