- Upon activation, 2-4 Blue Flies are spawned.
- Chemical Peel - The attack flies spawned by this item will deal increased damage if the last shot fired was a Chemical Peel shot.
- When combined with two other Guppy items, (Dead Cat, Guppy's Tail or Guppy's Paw), Isaac will turn into Guppy. He will also gain The Mulligan effect and flight.
- The item's icon from the original game is surrounded with flies.
- From the original game, when entering a door while/right after using Guppy's Head, the flies will not spawn.
|Abaddon • Cricket's Body • Cricket's Head • Experimental Treatment • Guppy's Collar • Guppy's Tail • Isaac's Heart • Maw of the Void • Roid Rage|
|Bob's Rotten Head • Book Of Revelations • Dead Sea Scrolls • Guppy's Head • Mega Blast • Monster Manual • Tammy's Head • The Bible • The Book of Belial • Yum Heart|
|Bob's Brain • Brother Bobby • Bumbo • Bum Friend • Dark Bum • Gemini • Key Bum • Lil Gurdy • Sister Maggy|
|A Snack • Breakfast • Dessert • Dinner • Lunch|