In this work, the thermal degradation of tropane and opium alkaloids was studied in samples of breadsticks prepared with corn flour, contaminated with seeds of Datura stramonium, and containing seeds of Papaver somniferum L. A total of seven different samples were prepared and eight alkaloids were studied, three tropane (atropine, scopolamine, and anisodamine) and five opium (morphine, codeine, thebaine, papaverine, and noscapine) alkaloids. For this purpose, a fast, easy and efficient method based on solid-liquid extraction (SLE) prior to the analysis by high-performance liquid chromatography with a diode array detector (HPLC-DAD) was developed and validated. Thermal degradation studies showed a decrease in the TAs and OAs content under baking (180 °C for 20 min) that was between 7–65% for atropine, depending on the preparation conditions used, between 35–49% for scopolamine and anisodamine, up to 100% for morphine and codeine and between 14–58% for thebaine, papaverine, and noscapine. Results also evidenced that degradation of morphine and codeine was higher when the seeds were added as topping to the breadsticks.