Medulloblastoma (MB) is an aggressive pediatric brain cancer mainly arising in the cerebellum, accounting for around 10 percent of central nervous system tumors. However, the available treatments often have undesirable side effects and are not always effective. To minimize the side effects, a crude seed extract (IBIL-AR1) was obtained from the plant Annona Reticulata and was found to be enriched with bioactive polyphenols. An MTT-based cell viability assay demonstrated that the IC50 value of IBIL-AR1 on DAOY cells (a medulloblastoma cell line) was 1.8 μg, whereas there is no adverse impact on the normal epithelial cell line, RWPE1. A decreased clonal formation was found in the treated DAOY cells compared to the untreated ones (P<0.001). Additionally, this novel drug reduces the size and number of medullospheroids, generated from DAOY cells and it has no impact on normal stem cells (mesenchymal cells; MSC). To determine the molecular mechanism, the expression of ABCC4 and REST was measured using Immunoblot analysis, as both proteins are found to be overexpressed in medulloblastoma cells. ABCC4 was found to be significantly (p<0.05) downregulated while there was not much difference in REST expression. We performed RNA sequencing to monitor the differential gene expression in medulloblastoma and the impact of IBIL-AR1. The results showed that there were more differentially expressed genes, and a heat map was created to demonstrate 422 significantly upregulated and 162 downregulated genes in IBIL-AR1-treated DAOY cells compared to the untreated ones. Therefore, current research demonstrated that IBIL-AR1 could be a potential therapeutic option for medulloblastoma. A future study will be performed to purify the lead compound(s) in IBIL-AR1 and evaluate their potential effects in a xenograft model.