AbstractFlexible pH sensors have attracted a great deal of attention in numerous applications, such as wearable healthcare devices, smart wound bandages, and other pH monitor sensors for chemical and bioprocess control. Herein, a facile approach to fabricate conducting polymer polypyrrole nanopillar arrays is proposed, and its potential as an advanced pH sensing interface is shown. Using oxygen plasma treatment as the etching tool, polypyrrole nanopillar/hair arrays can be prepared after etching 3D polypyrrole network structures. Conductive polypyrrole nanopillar arrays possessed unique advantages in sensing: their featured nanopillars has enhanced antibacterial properties; their structures showed excellent hydrophilicity and are favorable for interaction with analytes in small‐volume liquids. A flexible polypyrrole nanopillar array‐based potentiometric pH sensor integrated with a solid‐state reference electrode is further designed and fabricated. Superior performance with a near‐Nernstian response of 60.1±1.0 mV pH−1, excellent repeatability, high stability, and reproducibility is verified in the physiological pH range. The reliabilities of flexible and small‐volume sample testing, as well as the applicability for artificial sweat sample pH sensing, are examined. Provided with the advantages of antibacterial properties and hydrophilicity, the proposed flexible pH sensor is promising for trace analysis in biological, medical, and healthcare applications.