Surface-enhanced Raman scattering (SERS) is vital in many fields because of its high sensitivity, fast response, and fingerprint effect. The surface-enhanced Raman mechanisms are generally electromagnetic enhancement (EM), which is mainly based on noble metals (Au, Ag, etc.), and chemical enhancement (CM). With more and more studies on CM mechanism in recent years, non-noble metal nanomaterial SERS substrates gradually became widely researched and applied due to their superior economy, stability, selectivity, and biocompatibility compared to noble metal. In addition, non-noble metal substrates also provide an ideal new platform for SERS technology to probe the mechanism of biomolecules. In this paper, we review the applications of non-noble metal nanomaterials in SERS detection for biomedical engineering in recent years. Firstly, we introduce the development of some more common non-noble metal SERS substrates and discuss their properties and enhancement mechanisms. Subsequently, we focus on the progress of the application of SERS detection of non-noble metal nanomaterials, such as analysis of biomarkers and the detection of some contaminants. Finally, we look forward to the future research process of non-noble metal substrate nanomaterials for biomedicine, which may draw more attention to the biosensor applications of non-noble metal nanomaterial-based SERS substrates.