Ayyadurai worked as a consultant at Millennium Pharmaceuticals following his PhD.

Ayyadurai founded Systems Health, a company focused on personalized medicine based on systems biology. The company's focus was on providing insights into individual health through the analysis of complex biological systems. This venture reflects his background in biological engineering.

Ayyadurai established Email Invention, LLC, primarily to promote his claims related to the invention of email and to market related products and services. The company's activities are closely tied to his ongoing efforts to gain recognition as the inventor of email.

Founded CytoSolve, Inc., a company that offers computational modeling solutions for drug discovery. The technology is based on his prior research. This shows continued entrepreneurial efforts applying scientific research.