Salmonella is a potential feed safety hazard that is destroyed during rendering, but this does not eliminate the potential for cross contamination. The objective of this experiment was to evaluate the effectiveness of chemicals to mitigate Salmonella cross-contamination in rendered proteins. Treatments were arranged in a 6 × 4 factorial with 6 chemical treatments: (1) chemically negative control, (2) 0.3% commercial formaldehyde, (3) 2% essential oils (1:1 garlic, turmeric, capsicum, oregano, and rosemary), (4) 2% medium chain fatty acids (1:1 caproic, caprylic, and capric acid 1:1), (5) 3% organic acids (1:1 lactic, propionic, formic, and benzoic), (6) 1% sodium bisulfate in 4 rendered proteins: (a) feather meal, (b) blood meal, (c) meat and bone meal, and (d) poultry by-product meal. Matrices were chemically treated, then inoculated with Salmonella Typhimurium, and enumerated on d 0, 1, 3, 7, 14, 21, and 42 post-inoculation. Analyzed values represent colony forming units per gram (cfu/g). All main effects and interactions were significant (P < 0.05). Salmonella concentration in ingredients treated with medium chain fatty acid and commercial formaldehyde were similar to one another (P = 0.23), but 2 logs lower than the control (P < 0.05; 3.20 × 10⁰ and 4.45 × 10⁰ vs. 3.65 × 10² cfu/g, respectively). Ingredients treated with organic acid and essential oils had less Salmonella than the control (P < 0.05; 1.58 × 10¹ and 1.26 × 10² cfu/g, respectively). However, treating ingredients with sodium bisulfate resulted in similar Salmonella concentrations as the control (P < 0.05; 2.42 × 10² cfu/g). Time played a role in Salmonella mitigation as all days (P < 0.05) except d 14 and 21 (P = 0.92) were different from one another (3.14 × 10⁴, 4.48 × 10², 5.57 × 10¹, 8.98 × 10⁰, 3.07 × 0°, 3.16 × 10⁰, 1.35 × 10⁰ cfu/g for d 0, 1, 3, 7, 14, 21, and 42, respectively). Matrix also affected Salmonella stability as concentrations in meat and bone meal and blood meal and were similar to one another (P = 0.36; 6.54 × 10¹ and 5.32 × 10¹ cfu/g, respectively), but greater than (P < 0.05) levels in feather meal and poultry by-product meal (2.29 × 10¹ and 2.31 × 10¹ cfu/g, respectively). In summary, chemical treatment and time both mitigated Salmonella, but their effectiveness was matrix dependent. Chemical treatment with medium chain fatty acids or a commercial formaldehyde product was most effective at mitigating Salmonella in rendered protein meals.