This review explores the development and applications of microfluidic systems that utilize surface-enhanced Raman scattering (SERS) detection for disease diagnosis. SERS, a technique that leverages localized surface plasmon coupling to enhance the detection of target molecules, has been integrated with microfluidic technology to create highly sensitive and reproducible diagnostic tools. The review categorizes various SERS-based microfluidic devices, including continuous-flow channels, microarray-embedded channels, droplet microfluidic channels, digital droplet channels, and gradient microfluidic channels. Each type of device is discussed in detail, highlighting their unique features, advantages, and limitations. For instance, continuous-flow channels maintain homogeneous mixing conditions, while microarray-embedded channels enable multiplex detection of multiple targets. Droplet microfluidic channels address the memory effect issue by generating monodisperse droplets, and digital microfluidics (DMF) chips eliminate the need for external pumps and valves. Gradient microfluidic channels automate the generation of serial dilutions of target molecules. The review also discusses the challenges and future directions for translating these technologies into practical clinical applications, emphasizing the need for miniaturization, precise flow control, and integration with machine learning for enhanced diagnostic accuracy.This review explores the development and applications of microfluidic systems that utilize surface-enhanced Raman scattering (SERS) detection for disease diagnosis. SERS, a technique that leverages localized surface plasmon coupling to enhance the detection of target molecules, has been integrated with microfluidic technology to create highly sensitive and reproducible diagnostic tools. The review categorizes various SERS-based microfluidic devices, including continuous-flow channels, microarray-embedded channels, droplet microfluidic channels, digital droplet channels, and gradient microfluidic channels. Each type of device is discussed in detail, highlighting their unique features, advantages, and limitations. For instance, continuous-flow channels maintain homogeneous mixing conditions, while microarray-embedded channels enable multiplex detection of multiple targets. Droplet microfluidic channels address the memory effect issue by generating monodisperse droplets, and digital microfluidics (DMF) chips eliminate the need for external pumps and valves. Gradient microfluidic channels automate the generation of serial dilutions of target molecules. The review also discusses the challenges and future directions for translating these technologies into practical clinical applications, emphasizing the need for miniaturization, precise flow control, and integration with machine learning for enhanced diagnostic accuracy.