Plug-in fuel cell electric buses (PFCEBs) have the potential to effectively reduce energy usage through efficient energy management. However, when PFCEBs operate on non-fixed bus routes, noise factors such as driving cycle, stochastic vehicle mass, and driving distance make it challenging to achieve optimal fuel economy. To tackle this issue, this study introduces an adaptive energy management control method for PFCEBs operating on non-fixed bus routes, considering the aforementioned factors. Firstly, an adaptive energy management control method based on the algorithm of Pontryagin's Minimum Principle (PMP) is proposed to be integrated into the energy management system, allowing for real-world adaptive control. Secondly, a Design for Six Sigma (DFSS) methodology is proposed to address the noise disturbance problem caused by the driving cycle, stochastic vehicle mass, and driving distance. The main objective of DFSS is to find the "flat" zone of the design space (constituted by co-state and normalized distance), whilst minimizing the mean hydrogen consumption and its standard deviation. Validation results from Monte Carlo Simulation (MCS) demonstrate the effectiveness and applicability of the DFSS methodology in the energy management design for PFCEBs operating on non-fixed bus routes. Furthermore, simulation results indicate that the proposed robust co-state design method can achieve fuel economy comparable to that of an off-line PMP control strategy. In comparison to the rule-based strategy, the fuel economy improves by an average of 18.01%, 20.06%, and 18.91% for bus route 1, 2, and 3, respectively.