Stretchable thermoelectric-based self-powered sensors have attracted widespread attention for wearable electronic devices. However, the development of thermoelectric materials with wearable comfort, green, and multimodal synergy remains challenging. In this paper, we prepared a poly(3,4-ethylenedioxythiophene)/multi-walled carbon nanotube (PEDOT/MWCNT)-based thermoelectric fabric for self-powered strain–temperature dual-parameter sensing via spraying and in situ bio-polymerization. Compared with ferric chloride (FeCl3), used in chemical polymerization, the PEDOT thermoelectric fabric prepared by enzymatic polymerization is not doped with metal ions, making the thermoelectric performance of flexible wearable fabrics more stable. In addition, the energy-filtration effect of PEDOT and MWCNT efficiently enhanced the thermoelectric performance of the fabric. The fabric has over 320% elongation potential and excellent breathability while exhibiting excellent wearability. Moreover, the fabric-based sensor had a wide strain range (1–100%) and temperature detection limit (1 °C). In addition, fabric-based sensors were tested by sewing them directly onto clothing or attachment accessories, and showed a rapid response to changes in human joint bending and microenvironmental temperature differences. Moreover, the sensor could be integrated into an intelligent firefighting suit, to continuously and synergistically monitor health abnormalities in firefighter's body movement and temperature thresholds in the micro-environmental temperature of the suit. The developed self-powered dual-parameter wearable sensor shows fascinating potential for applications in human health monitoring, human–computer interaction devices, and intelligent robotics.