Ongoing research on the sensitivity and integration of refractive index‐based biosensors has resulted in significant advancements. Here, the study presents an enhanced surface plasmon resonance biosensor that integrates imaging technology and features dual‐parameter interrogation (intensity and phase) with guided mode coupling. By depositing a silica‐waveguide‐layer on a metal‐layer, two‐mode coupling is established to generate a high Q resonance and induce a phase mutation. The sensing performance experiment demonstrated a phase sensing sensitivity of 1.1 × 105 degree RIU−1, Q‐value of the resonant peak up to 314, and figure of merit of 300 RIU−1, superior to most standard plasmonic sensors. An in‐line phase‐polarization modulation scheme combined with imaging technology is proposed to extract the resonant phase carrying refractive index information. Additionally, a pair‐prism module is designed to optimize the sensing system configuration. Meanwhile, dual‐parameters interrogation including the intensity and phase are demonstrated, which offers potential for complementary and multi‐sensing fusion applications. The intensity interrogation also shows a considerable sensitivity of 7.2 × 104 a.u. RIU−1. Furthermore, it is combined with microfluidic chip to detect of alpha‐synuclein protein closely related to Parkinson's disease, and the limit of detection can reach 300 pg mL−1 level, which indicated a considerable potential for high‐throughput diagnosis application.