Increased thermal resistance of Salmonella at low water activity (a w) is a significant food safety concern in low-moisture foods (LMFs). We evaluated whether trans -cinnamaldehyde (CA, 1000 ppm) and eugenol (EG, 1000 ppm), which can accelerate thermal inactivation of Salmonella Typhimurium in water, can show similar effect in bacteria adapted to low a w in different LMF components. Although CA and EG significantly accelerated thermal inactivation (55 °C) of S. Typhimurium in whey protein (WP), corn starch (CS) and peanut oil (PO) at 0.9 a w , such effect was not observed in bacteria adapted to lower a w (0.4). The matrix effect on bacterial thermal resistance was observed at 0.9 a w , which was ranked as WP > PO > CS. The effect of heat treatment with CA or EG on bacterial metabolic activity was also partially dependent on the food matrix. Bacteria adapted to lower a w had lower membrane fluidity and unsaturated to saturated fatty acids ratio, suggesting that bacteria at low a w can change its membrane composition to increase its rigidity, thus increasing resistance against the combined treatments. This study demonstrates the effect of a w and food components on the antimicrobials-assisted heat treatment in LMF and provides an insight into the resistance mechanism. • Effect of the antimicrobial-assisted heat treatment reduces at lower water activity. • Bacterial resistance varies across different food matrices at the same water activity. • Treatment effect on bacterial metabolic activity varies across different matrices. • Changed membrane composition increases its rigidity at lower water activity. [ABSTRACT FROM AUTHOR]