Mathai is a given name or surname, and may refer to:
- John Mathai, economist who served as India's first Railway Minister and subsequently as India's Finance Minister
- Mathai, an Indian-American musician who was a contestant on season two of the American version of The Voice.
- Mathai Manjooran, Indian freedom fighter from Kerala
- Mathai Varghese, mathematician and an Australian Research Council Senior Research Fellow at the University of Adelaide
- O.M. Mathai, Special assistant of the Prime Minister of India Jawaharlal Nehru and author of two books