Nanomaterials-enhanced surface plasmon resonance (SPR) sensors have been developed to improve the sensitivity of detecting low molecular weight (less than 400 Da) biological and chemical analytes. Traditional SPR sensors are limited in sensitivity for detecting trace amounts of small molecules, such as cancer biomarkers, hormones, antibiotics, and explosive materials. Recent advances in nanotechnology have enabled the use of nanomaterials like metallic nanoparticles, magnetic nanoparticles, carbon-based nanomaterials, latex nanoparticles, and liposome nanoparticles to enhance SPR sensing. These nanomaterials improve sensitivity by enhancing electric fields, increasing surface mass loading, enabling charge transfer, improving adsorption efficiency, and providing catalytic activity. Gold nanoparticles (Au NPs) are particularly effective for enhancing SPR signals due to their strong absorption in the visible and near-infrared range. Au NPs can be functionalized with various molecules to improve selectivity and binding efficiency. Magnetic nanoparticles offer advantages such as lower production costs and the ability to be manipulated by external magnetic fields. Carbon-based nanomaterials like graphene also show promise for enhancing SPR signals. The review discusses various applications of nanomaterial-enhanced SPR sensors, including DNA and oligonucleotide detection, protein detection, and the sensing of harmful chemicals for food and environmental monitoring. These sensors have shown significant improvements in sensitivity and detection limits, with some achieving detection limits as low as 10 fM for DNA and 1 pM for proteins. The use of Au NPs in SPR sensors has been shown to enhance signal amplification and improve the detection of small molecules. The review also highlights the potential of these sensors in clinical applications such as early cancer diagnosis, food quality control, and drug screening. Overall, nanomaterial-enhanced SPR sensors offer a promising platform for ultrasensitive detection of small molecules in various biological and chemical applications.Nanomaterials-enhanced surface plasmon resonance (SPR) sensors have been developed to improve the sensitivity of detecting low molecular weight (less than 400 Da) biological and chemical analytes. Traditional SPR sensors are limited in sensitivity for detecting trace amounts of small molecules, such as cancer biomarkers, hormones, antibiotics, and explosive materials. Recent advances in nanotechnology have enabled the use of nanomaterials like metallic nanoparticles, magnetic nanoparticles, carbon-based nanomaterials, latex nanoparticles, and liposome nanoparticles to enhance SPR sensing. These nanomaterials improve sensitivity by enhancing electric fields, increasing surface mass loading, enabling charge transfer, improving adsorption efficiency, and providing catalytic activity. Gold nanoparticles (Au NPs) are particularly effective for enhancing SPR signals due to their strong absorption in the visible and near-infrared range. Au NPs can be functionalized with various molecules to improve selectivity and binding efficiency. Magnetic nanoparticles offer advantages such as lower production costs and the ability to be manipulated by external magnetic fields. Carbon-based nanomaterials like graphene also show promise for enhancing SPR signals. The review discusses various applications of nanomaterial-enhanced SPR sensors, including DNA and oligonucleotide detection, protein detection, and the sensing of harmful chemicals for food and environmental monitoring. These sensors have shown significant improvements in sensitivity and detection limits, with some achieving detection limits as low as 10 fM for DNA and 1 pM for proteins. The use of Au NPs in SPR sensors has been shown to enhance signal amplification and improve the detection of small molecules. The review also highlights the potential of these sensors in clinical applications such as early cancer diagnosis, food quality control, and drug screening. Overall, nanomaterial-enhanced SPR sensors offer a promising platform for ultrasensitive detection of small molecules in various biological and chemical applications.