[1] He is known for his work in nuclear magnetic resonance spectroscopy of lipids, proteins, and membranes; of inorganic solids; in computational chemistry, and in microbiology and parasitology.

He obtained a PhD in Biophysical Chemistry from the University of Sheffield in 1972, with Dennis Chapman, developing NMR methods to study lipid and membrane structure.

In the 1970s and 1980s Oldfield developed ways to investigate lipid and membrane structure including the use of 2H nuclear magnetic resonance (NMR) spectroscopy of labelled compounds.

[9] In the early 1970s, while working with Adam Allerhand, Oldfield reported the first high-resolution 13C NMR spectra of proteins—lysozyme, myoglobin and cytochrome c—in which numerous single carbon atom sites could be resolved and assigned.

He showed that high-resolution spectra of quadrupolar nuclei (such as 17O, 23Na) could be obtained by using variable-angle sample-spinning,[21] spin echo,[22] as well as spectral deconvolution methods.

Working in collaboration with Julio Urbina and Roberto Docampo, his group found, using 31P NMR spectroscopy, that the parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas disease, contained very high levels of diphosphate, and that diphosphate analogs, bisphosphonates used clinically to treat bone resorption diseases, killed these parasites.

The human pathogen Staphylococcus aureus contains a gold-colored virulence factor called staphyloxanthin that protects the bacterium from killing by reactive oxygen species.

[33] In 2012, Oldfield's group synthesized lipophilic analogs of the clinical bisphosphonate drugs zoledronate and risedronate, to prevent unwanted binding to bone mineral, and found they had potent anti-malarial activity.

[38] His group also showed that some clinically used bisphosphonate drugs are converted to analogs of adenosine triphosphate that function by inhibiting cell signaling pathways.