An emerging consumer trend to purchase minimally heated and ready-to-eat food products may result in processing methods that do not effectively reduce pathogenic populations. Crude Maillard reaction products (MRPs) are naturally generated compounds that have been shown to display antimicrobial effects against pathogens. Crude MRPs were generated from reducing sugars (fructose (Fru), glucose (Glc), ribose (Rib) or xylose (Xyl)) with lysine and the melanoidin equivalence was measured using an absorbance of 420 nm (Ab420). The relative antimicrobial activity of each MRP was measured by examining both the length of lag phase and maximum growth rate. MRPs were found to significantly shorten the lag phase and decrease the maximum growth rate of S. Typhimurium (p < 0.05). Glucose-lysine MRP (GL MRP) was determined to have the highest relative melanoidin (1.690 ± 0.048 at Ab420) and its efficacy against S. Typhimurium populations was measured at 37 °C and at pH 7.0 and estimated on xylose lysine deoxycholate (XLD) agar. GL MRP significantly reduced S. Typhimurium populations by >1 log CFU/mL at 8 and 24 h after inoculation (p < 0.05). GL MRPs also further decreased S. Typhimurium populations significantly under thermal stress condition (55 °C) compared to optimal (37 °C) by ~1 log CFU/mL (p < 0.05). Overall, GL MRP demonstrated effective antimicrobial activity against S. Typhimurium at 37 °C and 55 °C.