Traditional healthcare for chronic wounds and Cold Atmospheric Plasma (CAP) treatments relies on passive dressings and large-volume stationary equipment operating with open-loop systems, which severely limits their use and confines it to specialized clinical environments. To address the lack of active thermal safety mechanisms in mobile devices, this research proposes a wearable smart plasma patch equipped with a closed-loop adaptive electronic control system to ensure safe patient care and treatment at home. The smart patch integrates real-time analog biosensors to continuously monitor skin temperature and relative humidity. An algorithm running on a microcontroller dynamically adjusts the high-voltage plasma parameters using Pulse Width Modulation (PWM). The system's performance was rigorously verified using a combined simulation framework for mixed signals, with Proteus software for electronic circuits and MATLAB/Simulink for biodynamics and thermodynamics. The simulation results demonstrated the controller's high efficiency in maintaining a precise, optimal treatment environment (36–37 °C, humidity ∼60%) and preventing thermal accumulation. In addition, the effectiveness of an active hardware protection mechanism was demonstrated, with an emergency high-voltage cut-off successfully implemented within a standard 20-ms time window upon detecting thermal hazards. In conclusion, this compact and intelligent design effectively limits the risk of tissue thermal necrosis, providing a powerful and independent safety indicator in the design of modern, scalable medical devices.