In this work, our recent efforts in the development of label-free surface plasmon resonance (SPR) sensors for food safety monitoring and early cancer diagnostics will be reviewed. For instrumentation, a nanopattern-enhanced SPR platform has been developed and then integrated into an SPR imaging system with contrast polarization. Nanopatterns are generated with electron beam lithography (EBL), which allows for control over all aspects of the nanofeatures including diameter, separation distance, and height. For surface chemistry, an array of proteins (antibodies, single-chain Fvs, or antigens) has been developed via spotting on a dual functional carboxybetaine-based coating, which is not only highly resistant to protein adsorption even from 100% blood plasma, but also has abundant functional groups for protein immobilization. For food safety applications, we have been working on the simultaneous and quantitative detections of bacterial pathogens, viruses, and marine toxins in complex media including juices, milks, and shell fish extracts in collaboration with researchers from the U.S. FDA. For early cancer diagnostics, we have been working on the screening of biomarkers (either antigens or auto-antibodies) from clinical samples for ovarian and breast cancers in collaboration with researchers from the Fred Hutchinson Cancer Research Center.