Green milkweed contains cardiac glycosides, which can alter heart rate and cause severe consequences if ingested. Children are at higher risk due to their curiosity and lower body weight. Contact with the sap can lead to dermatitis—red, itchy, inflamed, or blistering skin.

Green milkweed is native to North America, where it is planted in gardens and is important for a variety of pollinators, including monarch butterflies. It is generally not considered to be invasive. However, it can spread laterally via rhizomes in addition to self-seeding. Furthermore, it grows readily in disturbed areas, including roadsides, ditches, and fields. It is also generally avoided by livestock. Minimizing disturbance and encouraging the growth of diverse native plants will prevent green milkweed from becoming established as a weed. Green milkweed is resistant to many herbicides but can be controlled by some herbicides such as glyphosate and imazapyr.

The best season for the removal of green milkweed is late spring or early summer, before the plant has had a chance to produce seed pods.