El-Sayed's research interests include the use of steady-state and ultra fast laser spectroscopy to understand relaxation, transport and conversion of energy in molecules, in solids, in photosynthetic systems, semiconductor quantum dots and metal nanostructures. The El-Sayed group has also been involved in the development of new techniques such as magnetophotonic selection, picosecond Raman spectroscopy and phosphorescence microwave double resonance spectroscopy. A major focus of his lab is currently on the optical and chemical properties of noble metal nanoparticles and their applications in nanocatalysis, nanophotonics and nanomedicine. His lab is known for the development of the gold nanorod technology. As of 2021, El-Sayed has produced over 1200 publications in refereed journals in the areas of spectroscopy, molecular dynamics and nanoscience, with over 130,000 citations.