The Spiders in the comic live to annoy Garfield. They sometimes walk around the house or dangle from the ceiling—and Garfield squishes them with rolled-up newspapers. This, of course, leads to several attempts by the spiders to get back at Garfield—surprisingly, successful in around half of the cases. Garfield does occasionally obtain help from the spiders, such as to get rid of an annoying fly. A spider by the name of Guido has been introduced. The spiders often lose battles to Garfield. However, at times, they try to be nice to the cat.
- Using a laser pen to make Garfield fall of the table.
- Taking Pooky as a hostage.
- Ruining Garfield's selfie.
- Imprisoning Garfield in a web.
- A group of spiders once managed to drag Garfield up in the air with their webbing, and then put a cactus below him before they drop Garfield. Garfield shown little concern, as he only mildly complained, "This will not end well"
- Hitting Garfield with a newspaper (this has happened twice).
- They have appeared 386 times, the 6th most appearances.
- Spiders barely appear in Garfield and Friends - one huge arachnid is imagined by Wade the Duck in The Thing in the Box episode.