Dig out the plants if you have only a few of them in the garden. Find the main stem and dig around it, removing the entire plant with roots. Take care not to leave any roots behind.
Remove any new sprouting plants as soon as they appear. This will keep the plant from spreading. The stems of deadly nightshade root easily as they creep on the ground. The plant also spreads with seed.
Use products containing glyphosate as a chemical control strategy, as recommended by the University of Minnesota Extension. Spray the plant thoroughly with the herbicide. Avoid soaking the soil around the plant.
Apply the herbicide at temperatures of 60 to 80 degrees Fahrenheit for best results. Avoid the use of chemicals on windy days to minimize the risk of the chemicals drifting to other plants. Do not use if rain is expected within the next 24 hours as this will reduce efficacy of treatment.
Watch for symptoms of the plant dying within three to 10 days of application. This is indicated by a noticeable yellowing and wilting of the plant. It often takes repeat applications of herbicides, every 10 to 14 days, to kill deadly nightshade completely.