Flexible pressure sensors are being studied intensively for applications such as smart wearables and health monitoring. While ensuring the excellent sensing performance, the reliability (durability and environmental resistance) of the sensors are also key indicators that determine whether they can be used in practice. In this research, a strategy to adjust the sensing performance and high reliability of the flexible pressure sensors by self-assembled conductive coating and bifacial microstructures (BM) is proposed. Polydimethylsiloxane/carbon nanotube films with BM are first modified to reduce the surface contact angle. Then poly(dimethyl diallyl ammonium chloride) (PDAC) and hydroxylated carbon nanotubes/carboxylated cellulose nanofibers/glycerol (CNT-OH/CNF-C/GL) are successively assembled on the BM surface to construct conductive coatings (PCCG). The sensor based on PCCG and BM (the PCCG-BM sensor) shows a high sensitivity (9.97 kPa−1), a wide detection range (0–330 kPa), and a fast response time (59 ms). The PCCG-BM sensor has excellent repeatability, and it still outputs stable current change signals after 240,000 pressure cycles. What’s more, the PCCG-BM sensor is treated with extreme environments such as bending, stretching, washing, and high pressure, and the sensor still maintains excellent performances. This preparation strategy provides a new perspective for the fabrication of high-performance and high-reliability flexible sensors.