Stretchable optical fiber sensors (SOFSs), which are promising and ultra-sensitive next-generation sensors, have achieved prominent success in applications including health monitoring, robotics, and biological–electronic interfaces. Here, we report an ultra-sensitive multi-functional optical micro/nanofiber embedded with a flexible polydimethylsiloxane (PDMS) membrane, which is compatible with wearable optical sensors. Based on the effect of a strong evanescent field, the as-fabricated SOFS is highly sensitive to strain, achieving high sensitivity with a peak gauge factor of 450. In addition, considering the large negative thermo-optic coefficient of PDMS, temperature measurements in the range of 30 to 60 °C were realized, resulting in a 0.02 dBm/°C response. In addition, wide-range detection of humidity was demonstrated by a peak sensitivity of 0.5 dB/% RH, with less than 10% variation at each humidity stage. The robust sensing performance, together with the flexibility, enables the real-time monitoring of pulse, body temperature, and respiration. This as-fabricated SOFS provides significant potential for the practical application of wearable healthcare sensors.