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Polyphemus is a Cyclops in Greek mythology. The name "Polyphemus" may also refer to:
- Polyphemus (Argonaut), another figure from Greek mythology
- Antheraea polyphemus, or Polyphemus moth, a giant silk moth of North America
- Polyphemus (crustacean), a genus of cladocerans
- Limulus polyphemus, the Atlantic horseshoe crab
- Mecynorhina polyphemus, a species of beetle
- Polyphemus (book), a collection of short stories by Michael Shea
- Polyphemus (Reni), a 1639–1640 painting by Guido Reni
- Polyphemus (sculpture), an 1888 bronze by Auguste Rodin
- Polifemo (1735), an Italian opera by Nicola Porpora
- Polyphème (1922), a French opera by Jean Cras based on a 1902 verse play by Albert Samain
- The name of the gas giant in the Avatar series, which Pandora orbits