This study monitored the growth, biochemical, and developmental responses of Datura seedlings to the cold plasma. The effectiveness of different methods was explored to break seed dormancy. Germinating seeds were exposed to corona discharge plasma for different durations, including 0, 60, 120, 180, and 300 s. A procedure consisting of illumination with a red light (20 min), soaking in water (4°C for 48 h), and removing a part of Testa was the best method for breaking seed dormancy. The plasma treatments of 60, 120, and 180 s improved the plant growth performance, while this trait was declined in response to the plasma treatment of 300 s. The proline concentrations in both root and leaves displayed a linear significant upward trend in response to the plasma treatments. The plasma for 180 s was the most effective method to increase tropane alkaloids. With increasing the exposure time from 60 to 300 s, the leaf soluble phenols were linearly enhanced. The plasma application for 60, 120, and 180 s significantly augmented total protein concentration, while the exposure of seeds for 300 s significantly diminished it. The highest amounts of photosynthetic pigments (chlorophylls and carotenoids) were recorded in the seedlings treated with plasma for 120 and 180 s. The activities of enzymatic antioxidants (catalase and peroxidase) showed a similar upward trend to that of proline. The plasma priming also improved the phenylalanine ammonia‐lyase activity (a secondary metabolism index). Further investigations are needed to optimize plasma parameters and understand the involved mechanisms to maximize its benefits while minimizing potential risks.