Ellagic acid (EA) and Annona Muricata (AM) have antioxidant, anticarcinogenic and antiviral activity demonstrated by in vitro models. This pilot study investigated the in vivo potential anti-viral activity in women affected by Low squamous intraepithelial lesion (L-SIL) related to high risk human papilloma virus (HR-HPV), and the ability to modify the oncoproteins expression in the cervical lesion thickness. Sixty women affected by HR-HPV related L-SIL, were randomly divided into two groups: group A (n = 30) supplemented with EA (16 mg) + AM (100 mg) 2 times daily for 6 months and group B (n = 30) administered with placebo. HR-HPV clearance was obtained in 74% of cases in group A compared to 25% of cases in group B (p = 0.001) and p21 expression in LSIL thickness increased in 63.2% of cases in group A compared to 20% in group B (p = 0.03). AE/AM supplementation significantly induces HR-HPV elimination and stimulates p21 expression in LSIL thickness.