He was born on January 10, 1886, as the son of Challiyal Thomas Matthai and Anna Thayyil to an Anglican Syrian Christian family.

His nephew, Verghese Kurien, is generally recognized as the architect of India's White Revolution.

[9] Dr. John Matthai Centre,[10] Thrissur, located on the large plot of land donated by his family, is named in his honour.

His wife, Achamma Matthai was an Indian social worker and a women's rights activist.

[14] NCAER, led by the President of its Governing Body, Nandan Nilekani and with support from the Nilekani Philanthropies, honoured John Matthai in 2019 by naming NCAER's new office building at its campus in New Delhi as the John Matthai Tower.