DeGraffenreid is a surname. People with the surname include:
- Emma DeGraffenreid, plaintiff of a 1976 employment discrimination lawsuit cited in the development of the theory of intersectionality
- Gordon DeGraffenreid, American football coach
- Kenneth E. deGraffenreid, American university professor
- Reese C. De Graffenreid (1859–1902), American politician from Texas
- Veronica Degraffenreid, Secretary of the Commonwealth of Pennsylvania beginning in 2021
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