Malignant primary brain tumours are reported to be the leading cause of death from solid tumours in children and the third leading cause of death from cancer in adolescents and adults. Current treatment options include surgery, radiation and chemotherapy. Despite these treatment options, patient survival still remains poor. The Amaryllidaceae family contains alkaloids which have shown several biological activities including the treatment of Alzheimer's disease. This study investigates the cytotoxic activity of the methanolic extracts of fourteen plants belonging to the Amaryllidaceae family in brain tumour cell lines. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay was used to determine the effects of plant extracts on cell viability while routine antioxidant assays were conducted to determine the antioxidant activities of the extracts. Results showed that of the fourteen extracts, five (Cyrtanthus breviflorus, Amaryllis belladonna, Crinum variabile, Haemanthus pubescens, Nerine filifolia) showed cytotoxicity in all the cell lines tested with IC50 values under 100 µg/mL. Six extracts (Crinum moorei, Clivia miniata, Haemanthus amarylloides, Crossyne guttata, Nerine humilis, and Ammocharis longifolia) showed varying levels of cytotoxicity in the cell lines tested and were unable to induce 50% reduction in cell viability across the cell lines tested at the highest concentration of 100 µg/mL. Furthermore, three plant extracts (Brunsvigia bosmaniae, Boophone disticha, Strumaria truncata) had minimal or no cytotoxic effects on all cell lines tested when compared to control. The extracts also showed varying degrees of antioxidant activity but were not as potent as the positive control. Findings from this study suggest that species of the Amaryllidaceae family may be useful sources of phytochemicals for the treatment of central nervous system cancers and should be further explored in animal models of central nervous system (CNS) and other cancer types.