The tuber necrotic strain of Potato virus Y (PVYNTN) causes widespread disease and has severe negative effects on the growth and yields of plants, especially those of the Solanaceae family. The consequences of residual toxicity and non-biodegradation of synthetic chemicals and pollution of the environment has led to investigations into new non-toxic and biological treatments to control plant viral diseases. Ethanolic extracts of Bowiea volubilis (bulbs), Cotyledon orbiculata (leaves), Gomphocarpus fruticosus (leaves), Merwilla plumbea (dry and fresh bulbs), Nerium oleander (leaves), and the fruits and leaves of Strophanthus speciosus, were evaluated against PVYNTN in vivo and in vitro. At a concentration of 20 mg · ml−1, ethanolic extracts of Strophanthus speciosus (leaves) and fruits (50 mg · ml−1) significantly reduced the expression of PVYNTN symptoms on tobacco plants in vitro without affecting the normal growth and development of the plant. Similarly, at 50 mg · ml−1, N. oleander, C. orbiculata and B. volubilis (fresh bulbs) and S. speciousus leaves at 20 mg · ml−1 extracts showed significant differences in PVYNTN symptoms in the in vivo experiment. Strophanthus speciosus leaf and fruit extracts showed significant inhibition in the in vitro and in vivo assays and demonstrated that S. speciosus has potential to be used as an antiphytoviral treatment.