R21, R-21 or R.21 may refer to:
- In military
- HMAS Melbourne (R21), a 1945 Australian Royal Navy ship of the Majestic class of light aircraft carrier
- R-21 (missile), a submarine-launched ballistic missile developed and deployed by the Soviet Union
- USS R-21 (SS-98), a 1918 R-class coastal and harbor defense submarine of the United States Navy
- In transportation
- R21 (New York City Subway car)
- R21 road (Senegal)
- R21 (Gauteng), a road in South Africa
- Renault 21, a large family car produced between 1986 and 1994
- In science and academia
- R21: Harmful in contact with skin, a risk phrase in chemistry
- Dichlorofluoromethane, a hydrochlorofluorocarbon used as a propellant and refrigerant
- NIH Exploratory/Developmental Research Grant Award, a type of United States National Institute of Health grant
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