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- 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.