Sixspotted orbweaver has a method of defense or predation that involves delivering venom through a bite with its fangs. Typically, the toxicity experienced by animals such as humans or dogs is mild, but the intensity of the reaction can vary among different species. Frogs, which are generally more sensitive, might experience a stronger reaction to the venom. For insects, the toxic effects can be much more pronounced, possibly resulting in paralysis or death.

Sixspotted orbweaver is not characteristic of biting humans. Typically, sixspotted orbweaver would only bite in self-defense, and since it has mild venom, the impact on humans would be insignificant. Bites are rare and usually result from inadvertent contact.

Sixspotted orbweaver, by nature, prefers to avoid confrontations and only bites when provoked and in self-defense. Human encounters with sixspotted orbweaver are typically accidental due to the creature's tendency to inhabit areas frequented by people, such as gardens or homes. The rarity of bites and their non-lethal nature often result from inadvertent contact rather than aggression from sixspotted orbweaver.

To minimize the chances of an accidental encounter with sixspotted orbweaver, keep living spaces clean and free of clutter where sixspotted orbweaver may hide. Regularly dusting and vacuuming corners and secluded spaces can discourage sixspotted orbweaver from settling in human-inhabited areas. Use of window and door screens will further prevent entry into homes.

In the rare case of experiencing discomfort from an encounter with sixspotted orbweaver, the primary measure is to clean the affected area with soap and water to prevent any potential irritation. Following this, applying a cold compress can help with soothing any mild symptoms. Educating individuals on where sixspotted orbweaver is commonly found can lead to increased awareness and avoidance of accidental contact. During the recovery period, maintaining cleanliness and monitoring for any changes is advisable.