Sesamum angustifolium (Oliv.) Engl. and Hibiscus articulatus contain compounds that have antimutagenic properties. The rise in rhabdomyosarcoma in paediatrics and prognosis of the disease in infants compared to adults calls for newer, less toxic alternatives in treatment of the disease. The aim of this study was to determine the anticancer activity and antioxidant capacity of combined leaf extracts of Sesamum angustifolium (Oliv.) Engl. and Hibiscus articulatus (SAHA), against rhabdomyosarcoma (RMS) using rhabdomyosarcoma (RD) cell line and mouse (L20B) cell line. Cytotoxicity, morphology, apoptosis induction, and antioxidant capacity assays were done. Of the four solvents used for extraction, the dichloromethane SAHA extract was the most cytotoxic with IC50 of 106 μg/mL after doxorubicin, the reference anticancer drug with IC50 of 0.8 μg/mL. The SAHA extracts had a stronger cytotoxicity effect on the cancerous RD cells than on normal L20B cells. Morphological assessment showed untreated cells maintained their normal striated appearance of muscle cells whereas cells treated with doxorubicin or SAHA extracts exhibited cell shrinkage, loss of surface adherence, reduced cell density along with cell debris, which is a characteristic of apoptosis. Normal L20B cells when treated with doxorubicin or SAHA extracts, maintained their cell shape, and remained adherent to the surface. The apoptotic enzyme caspase-3 was induced in a concentration dependent manner upon treatment of the RD cells with SAHA extracts or doxorubicin. Induction of caspase-3 was ten times less in treated L20B cells compared to the RD cells. Low induction of caspase-9 enzyme was observed in both treated RD and L20B cells. Treatment of both RD and L20B cells with SAHA extracts or doxorubicin resulted in increased activity of peroxidase and reduction of oxidative stress. Results of the study show that the SAHA extracts are potential sources of compounds that may serve as useful agents for treatment of rhabdomyosarcoma.