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Dichapetalum madagascariense Poir (Dichapetalaceae) is traditionally used to treat bacterial infections, jaundice, urethritis and viral hepatitis in Africa. Its root contains a broad spectrum of biologically active dichapetalins. To evaluate the plant's effect on human MCF-7 cells and its' antibacterial and antiparasitic potentials, we isolated and identified the known dichapetalins A and M from the roots. Both dichapetalins were tested on six bacterial strains (Shigella flexneri, Bacillus cereus, Salmonella paratyphi B, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus) and two parasite strains; Trypanosoma brucei brucei, and Leishmania donovani using the Alamar Blue assay system. Dichapetalins A and M were more potent against B. cereus with IC50 values of 11.15 and 3.15 μg/ml, respectively, compared to the positive control ampicillin (IC50 = 19.50 μg/ml). Dichapetalins A (IC50 = 74.22 μg/ml) and M (IC50 = 72.34 μg/ml) were less active against T. b. brucei, compared to the standard Suramin (IC50 = 4.96 μg/ml). Dichapetalin M showed moderate activity against L. donovani (Amphotericin B: IC50 = 0.21 μg/ml) with an IC50 of 16.80 μg/ml. In human MCF-7 cells expressing the NR1I2 receptor, the activity of dichapetalin M was higher (IC50 = 4.71 μM and 3.95 μM) for 48 and 72 h of treatment, respectively compared to Curcumin with IC50 of 17.49 μM and 12.53 μM for 48 and 72 h of treatment, respectively. Results from in vitro expression studies with qPCR confirmed an antagonistic effect of dichapetalin M on PXR (NR1I2) signaling; supporting the PXR signaling pathway as a possible mode of action of dichapetalin M as predicted by in silico results. These findings confirm previous studies that D. madagascariense can be a source of potential lead compounds for development of novel antibiotic, antiparasitic and anticancer medicines, and provide further insights into the mechanism of action of the dichapetalins.