Salmonella enterica can survive well in low water activity foods, and therefore, causes frequent salmonellosis outbreaks in these products. Methods are needed to overcome such desiccation-resistant Salmonella to improve the safety of low aw foods. The purpose of the current work is to (a) screen natural food additives for ability to compromise the desiccation resistance in S. enterica, and (b) assess the ability of a selected membrane-active additive to inactivate S. enterica during milk spray drying and freeze drying. To accomplish this, 10 food additives, at different concentrations ranged from sublethal to lethal levels, were screened for ability to cause leakage of potassium ions from desiccation adapted S. enterica using a potassium-binding probe. Based on the screening results, the two additives, carvacrol and thymol, were assessed at 200 and 100 ppm, respectively, for their capability to sensitize S. enterica strains to mild heat treatment at 55°C for 15 min. Furthermore, carvacrol at levels of 200 to 5000 ppm was added to liquid milk samples inoculated with S. enterica cells to assess the pathogen inactivation during spray or freeze drying. Salmonella survivors were enumerated in milk powder immediately following the drying process and during storage of the milk powder at room temperature. Data were analyzed in GraphPad software. Results showed that the membrane active carvacrol and thymol caused potassium leakage (P<0.05) from desiccation adapted S. enterica strains. Carvacrol (200 ppm) and thymol (100 ppm), combined with heat treatment, reduced desiccation adapted Salmonella by 3.1±0.21 5.5 log CFU/mL compared to sole heat treatment (2.4±0.53 3.2±0.11 log CFU/mL reduction). Addition of carvacrol at 500 or 5000 ppm during spray or freeze-drying lowered Salmonella populations in milk powder by 1.3±0.1 to more than 4.5 log CFU/g, respectively. In conclusion, carvacrol is a potent food additive capable of combating desiccation resistant Salmonella and thus may improve safety of low water activity foods.