This paper reports a digital micro-mirror device (DMD)-enabled real-time multi-channel biosensing system based on angular interrogation surface plasmon resonance (SPR). In the experiments, angular scanning is achieved by a DMD that facilitates SPR measurements using a single-point photodetector. In the four-channel measurement setup, real-time monitoring of bovine serum albumin (BSA) and anti-BSA binding interactions is performed at various concentration levels. The experimental results have verified that the system has a resolution of 3.54 × 10-6 RIU (refractive index unit); and a detection limit of 9 ng/mL. The new DMD-based SPR interrogation system presents a new design route for practical solid-state SPR biosensing with a user-selectable range of interrogation, enhanced signal-to-noise ratio, and fast data throughput.