Physalis angulata is a medicinal plant with many benefits, which is used for the treatment of infertility related issues in traditional medicine. This study seeks to assess the prophylactic effect of Physalis angulata fruit extract on Hormone-induced uterine fibroids in Wistar rats. 60 animals were randomly divided into ten groups. The groups were as follows: Group I- Control group received distilled water for 6 weeks. Group II - Animals were induced with uterine fibroid by administering Diethylstibesterol (1.35 mg/kg/d) every day for 6 weeks orally using oral gavage, Progesterone injection of 1.0mg/180g in intramuscularly three times a week (Monday, Wednesday and Friday) for 5 weeks. 0.9 mg/kg/d adrenal hydrochloride injection was given intramuscularly in the last two weeks of the experiment. Group III, IV - animals were treated with 500 mg/kg and 1500 mg/kg body weight of Physalis angulata fruit extract respectively for 6 weeks respectively before inducement of fibroids for 6 weeks. Group V, VI - 500 mg/kg and 1500 mg/kg of body weight of fruit extract respectively daily for 6 weeks, Group VII- received Mifepristone only. Plant extracts were administered orally using oral gavage. Animals were sacrificed 24 hours after the last administration. Photochemical studies, gross morphology of the uterus, histological assessment of the uterus using H and E stains, apoptotic assessments were carried out using BAX and BCL2 and hormonal assay were assessed. Results showed increased levels of estrogen (16.38±0.80) and progesterone (9.66±0.58) in fibroid induced group which was reduced in low dose prophylactic groups (Estrogen= 10.99, Progesterone = 6.59) and high dose prophylactic groups (Estrogen= 10.33, Progesterone = 6.33) P≤0.05. Histopathological changes were observed in the uterus. Increased apoptotic marker reaction was seen in the low dose prophylactic group. The study successfully reduced the development of the uterine fibroid, evident by reduction of the uterine horn