S100 or S-100 may refer to:
- S-100 bus, an early computer bus
- S-100, an International Hydrographic Organization standard
- S100 protein, low-molecular-weight proteins in vertebrates
- The road number used in the Netherlands for inner-city ring roads
- AVE Class 100, or S100, a high speed train
- Canon PowerShot S100, a camera
- Colyaer Freedom S100, a Spanish amphibious ultralight aircraft
- Colyaer Gannet S100, a Spanish ultralight flying boat
- Colyaer Martin3 S100 is a Spanish ultralight aircraft
- A class of WWII German E-Boat.
- Guild S-100, an electric guitar
- Lenovo IdeaPad S100, a netbook computer
- Qtek S100, a mobile phone
- Schiebel Camcopter S-100, an unmanned aerial vehicle
- Škoda 100, a 1970s car
- USATC S100 Class, a 1942 steam locomotive class