Challenges exist in current flexible waveguide devices, such as the fabrication difficulties, mechanical flexibility limitation, and poor reliability. Based on the neutral-plane theory, flexible multimode polymer waveguides with a sandwich structure are designed and fabricated on the polyimide (PI) substrate. The flexible waveguide is endowed with excellent structural reliability and mechanical flexibility by constructing multiple neutral surfaces. The resultant flexible multimode optical polymer waveguides exhibit lower propagation loss (0.16 dB/cm at 850 nm) and lower inter-channel crosstalk (<-40 dB). Excellent mechanical bending property of the flexible waveguides (bending radius less than 3 mm) is also achieved by using micron-mechanical designs to minimize strain exerted on the waveguide core layer during mechanical deformation process. The transmission loss is not significantly increased when the bending radius is 1 mm and the bending is repeated 1000 times. Besides, the reliability test results reveal that the optimized flexible waveguide has excellent thermal stability, aging resistance, and machinability, for which, the resultant flexible waveguides show no performance degradation after humidity cycling, temperature cycling,and lead-free reflow soldering tests. Hence, this work provides theoretical and technical guidance for the practical mass-production of high quality flexible polymer waveguides with excellent mechanical flexibility and environmental reliability.