Background: Conventional chemotherapy is often limited by toxicity and drug resistance. Maerua angolensis DC., used in traditional African medicine, represents an underexplored source of potential anticancer agents. This study characterized the phytochemistry and cytotoxicity of a methanolic leaf extract from M. angolensis against human breast (MCF-7) and colorectal (HT-29) adenocarcinoma cells. Methods: The extract was subjected to qualitative phytochemical screening and Gas Chromatography-Mass Spectrometry (GC-MS) analysis. Cytotoxicity was evaluated using the MTT assay after 24-hour treatment, with doxorubicin and capecitabine as positive controls. Morphological changes were assessed via Hematoxylin and Eosin (H&E) staining, and IC₅₀ values were determined by nonlinear regression. Results: Phytochemical analysis identified flavonoids, tannins, and cardiac glycosides. GC-MS revealed 22 compounds, predominantly oleic acid (29.51%), palmitic acid (21.87%), linoleic acid (12.34%), and stigmasterol (8.76%). The extract demonstrated moderate, concentration-dependent cytotoxicity. Against MCF-7 cells, the extract IC₅₀ was 15.6 ± 2.5 µg/mL, while doxorubicin was 15.6-fold more potent (IC₅₀ 1.0 ± 0.18 µg/mL; p<0.0001). Against HT-29 cells, the extract IC₅₀ was 34.4 ± 2.5 µg/mL, compared to a 3.4-fold more potent capecitabine (IC₅₀ 10.0 ± 2.0 µg/mL; p<0.0001). H&E staining confirmed concentrationdependent apoptotic morphology, with MCF-7 cells showing greater sensitivity. Conclusion: M. angolensis leaf extract, rich in bioactive fatty acids and phytochemicals, exhibits moderate in vitro cytotoxicity against breast and colorectal cancer cells, inducing apoptotic morphological changes. The IC₅₀ values fall within a biologically relevant range for natural products. These findings validate its traditional use and provide a strong rationale for further mechanistic and in vivo studies to explore its potential complementary role in cancer therapy.