Flexible strain sensors have gained prominence in applications such as wearable devices, smart healthcare, and human motion monitoring due to their excellent adaptability and sensitivity. However, challenges such as high production costs and complex fabrication processes hinder their widespread commercial adoption. This study presented a fatigue-resistant polystyrene (PS) microsphere nanoarray optical strain sensor based on a polydimethylsiloxane flexible substrate, fabricated using a simple hemispherical indentation-assisted method. The sensor exhibited exceptional stability, enduring over 950 cycles, and demonstrated remarkable durability and sensitivity (−0.371 nm/ %) at stretching speeds of 62.5 μm/s. Finite element analysis, supported by the experimental data, clarified the mechanical behavior of PS nanoarrays under varying strain angles and analyzed the influence of these angles on the sensing spectrum. Besides, fatigue points caused by repeated use could be naturally recovered, with the restored sensor maintaining excellent stability. The results suggested that this proposed flexible nanostructure offered a high-performance, cost-effective, and straightforward manufacturing option for strain optical sensors.