Black-leg nephila uses its sting to subdue prey primarily for reproductive purposes. The venom can exert a range of effects, from mild to severe paralysis, on its targeted invertebrates such as cockroaches, which it uses to provide a live food source for its larvae. Exposure to its sting leads to different degrees of immobilization, ensuring the survival of black-leg nephila's offspring. Although the sting is mainly a threat to insects, other animals generally do not encounter significant risk from black-leg nephila.'s defensive behavior.

Black-leg nephila generally do not bite humans, as they are not aggressive towards people. On the rare occasions these bites occur, they are typically a defense mechanism against perceived threats. The bite of black-leg nephila is not harmful, causing minor symptoms similar to a bee sting.

Black-leg nephila are not inherently dangerous to humans, but their presence can cause distress. They typically set up their webs in areas frequented by people. An accidental encounter with a web or the spider itself might trigger a defensive bite, although this is rare and usually only results from direct provocation or mishandling.

To prevent issues with black-leg nephila, regular cleaning of indoor spaces and maintenance of outdoor areas is helpful. This includes knocking down any visible webs and ensuring that dense vegetation near living spaces is well-trimmed. Discouraging their presence through the use of natural repellents like eucalyptus or peppermint oil can also be effective.

In the event of an encounter with black-leg nephila leading to discomfort, keep the affected area clean and use a cold compress to soothe any minor irritation. Distraction techniques such as engaging in activities or listening to music may also help in reducing distress. It's important to stay calm and avoid disturbing the web or black-leg nephila further. Those with persistent symptoms should consult a professional for non-medical interventions and further advice on reducing discomfort.