The present study describes the bioactivity guided isolation and structural elucidation of novel anticancer compounds from the Bangladeshi medicinal plant Blumera lacera. At the outset nineteen Bangladeshi medicinal plants were selected and collected from different parts of Bangladesh. Plants underwent preliminary cytotoxicity screening based on their traditional medicinal uses, limited previous research on them, and their availability. The selected plants were extracted with methanol and screened for their cytotoxic potential using the MTT assay against two healthy cell lines (mouse fibroblast (NIH3T3), a healthy monkey kidney (VERO)) and four cancer cell lines namely, gastric (AGS), colon (HT-29), two breast (estrogen-dependent: MCF-7 and estrogen non-dependent: MDA-MB-231). Preliminary cytotoxicity assessment led to the identification of seven plants with significant cytotoxic potential, having IC50 < 1.0 mg/mL against a minimum of one cancer cell line. The identified plants were: Avicennia alba, Caesalpinia pulcherrima, Diospyros peregrina, Ecbolium viride, Jasminum sambac, Clitoria terantea, and Saraca asoca. The bioactivity detected correlated with their traditional uses as anticancer agents. Comparing cytotoxicity effects of the selected plants with that of Blumea lacera which was previously screened for cytotoxic potential in our research lab, Blumea lacera was found to be more cytotoxic and thus selected for bioassay-guided isolation of constituents.