The four-spot orb-weaver uses its fangs to inject venom, functioning for both predation and defense. Its venom is mild and often leads to minor reactions in animals such as humans, dogs, and cats, who may experience local discomfort or slight swelling. Meanwhile, smaller mammals might have more pronounced reactions due to their size. Insects, being much smaller, could suffer more serious consequences from the venom, which can swiftly immobilize them. Adult four-spot orb-weaver possess this capability and are the life stage typically responsible for the secretion of toxins.

Four-spot orb-weaver typically does not bite humans. Bites are rare, occurring primarily in self-defense when the spider feels threatened. If a bite happens, it generally uses its fangs to deliver a mild and normally harmless bite, with immediate effects including minor irritation and localized pain.

Four-spot orb-weaver typically cohabit spaces that humans occupy, such as gardens, homes, or forests. Trouble arises as a result of accidental encounters between humans and four-spot orb-weaver. Since four-spot orb-weaver bites only occur defensively and not out of predation, the likelihood increases when humans inadvertently disturb their webs or threaten their safety, leading to the rare instances of bites causing minor irritation.

To prevent problems with four-spot orb-weaver, individuals should be cautious around areas where four-spot orb-weaver might live. Keeping living spaces clean, reducing clutter, and sealing cracks or gaps in walls can minimize unintentional encounters. Regularly checking and clearing spaces such as garages, sheds, and under furniture for webs can discourage four-spot orb-weaver from settling in human-occupied areas.

In the unusual event of a four-spot orb-weaver bite, the reaction is normally mild. Washing the area with soap and water can help to keep it clean. For symptom relife, a cold compress can be applied to reduce swelling or irritation. It is generally advisable to minimize disturbance of the affected area. During recovery, ensure the bitten area is kept clean and monitor for any changes; if symptoms persist or worsen, seeking professional advice is recommended.