Plasmon-enhanced luminescence (PEL) is a unique photophysical phenomenon in which the interaction between luminescent moieties and metal nanostructures results in a marked luminescence enhancement. PEL offers several advantages and has been extensively used to design robust biosensing platforms for luminescence-based detection and diagnostics applications, as well as for the development of many efficient bioimaging platforms, enabling high-contrast non-invasive real-time optical imaging of biological tissues, cells, and organelles with high spatial and temporal resolution. This review summarizes recent progress in the development of various PEL-based biosensors and bioimaging platforms for diverse biological and biomedical applications. Specifically, we comprehensively assessed rationally designed PEL-based biosensors that can efficiently detect biomarkers (proteins and nucleic acids) in point-of-care tests, highlighting significant improvements in the sensing performance upon the integration of PEL. In addition to discussing the merits and demerits of recently developed PEL-based biosensors on substrates or in solutions, we include a brief discussion on integrating PEL-based biosensing platforms into microfluidic devices as a promising multi-responsive detection method. The review also presents comprehensive details about the recent advances in the development of various PEL-based multi-functional (passive targeting, active targeting, and stimuli-responsive) bioimaging probes, highlighting the scope of future improvements in devising robust PEL-based nanosystems to achieve more effective diagnostic and therapeutic insights by enabling imaging-guided therapy.