Polyamines, including putrescine, spermidine, and spermine, are biological compounds present in nearly all food items. Their desirable physiological effects include cell division and growth. Hence, are undesirable in the diet of patients with tumor. This study aimed to assess the impact of curing agents (sodium chloride (0–2 g), sodium nitrite (0–200 ppm), sodium polyphosphate (0–0.5 g), and ascorbic acid (0–500 ppm)), cooking (frying (180°C), and boiling (100°C)) on polyamine contents in turkey breast meat using response surface methodology based on central composite design and dispersive liquid-liquid microextraction. Postprocessing changes were investigated using a high-performance liquid chromatography equipped with an ultraviolet detector. Study outcomes showed the presence of sodium chloride, sodium nitrite, and sodium polyphosphate in turkey meat reduced the putrescine and spermine content significantly (P < 0.0001). The addition of ascorbic acid as a curing agent slightly increased the concentration of polyamines, while no significant linear effects were associated with the thermal processes. The study observed that curing agents like sodium chloride, sodium nitrite, sodium polyphosphate, and ascorbic acid at 2 g, 200 ppm, 0.5 g, and 382 ppm, respectively, in frying mode minimized spermine and putrescine content with more than 96% desirability. In conclusion, curing additives and cooking are promising procedures for polyamine reduction in turkey breast meat.